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Drug Details
01. General Information
Name Sorafenib
PubChem CID 216239
Molecular Weight 464.8g/mol
Synonyms

Sorafenib, 284461-73-0, Nexavar, BAY 43-9006, sorafenibum, 4-(4-(3-(4-CHLORO-3-(TRIFLUOROMETHYL)PHENYL)UREIDO)PHENOXY)-N-METHYLPICOLINAMIDE, 4-[4-({[4-chloro-3-(trifluoromethyl)phenyl]carbamoyl}amino)phenoxy]-N-methylpyridine-2-carboxamide, Sorafenib free base, 4-[4-[[4-chloro-3-(trifluoromethyl)phenyl]carbamoylamino]phenoxy]-N-methylpyridine-2-carboxamide, 100012-18-8, UNII-9ZOQ3TZI87, 9ZOQ3TZI87, BAY-43-9006, N-(4-Chloro-3-(trifluoromethyl)phenyl)-N'-(4-(2-(N-methylcarbamoyl)-4-pyridyloxy)phenyl)urea, 4-(4-((((4-Chloro-3-(trifluoromethyl)phenyl)amino)carbonyl)amino)phenoxy)-N-methyl-2-pyridinecarboxamide, DTXSID7041128, CHEBI:50924, HSDB 8173, 4-[4-[[4-chloro-3-(trifluoromethyl)phenyl]carbamoylamino]phenoxy]-N-methyl-pyridine-2-carboxamide, 284461-73-0 (free base), MFCD06411450, BAY43-9006, CHEMBL1336, 4-[4-[[[[4-chloro-3-(trifluoromethyl)phenyl]amino]carbonyl]amino]phenoxy]-N-methyl-2-pyridinecarboxamide, 4-{4-[({[4-CHLORO-3-(TRIFLUOROMETHYL)PHENYL]AMINO}CARBONYL)AMINO]PHENOXY}-N-METHYLPYRIDINE-2-CARBOXAMIDE, EC 608-209-4, BAY-439006, Sorafenib [INN], 2-Pyridinecarboxamide, 4-(4-((((4-chloro-3-(trifluoromethyl)phenyl)amino)carbonyl)amino)phenoxy)-N-methyl-, Sorafenib (Nexavar), SORAFENIB (MART.), SORAFENIB [MART.], 4-(4-{3-(4-Chloro-3-(trifluoromethyl)phenyl)ureido}phenoxy)-N(sup 2)-methylpyridine-2-carboxamide, Donafenib (Sorafenib D3), 2-Pyridinecarboxamide, 4-[4-[[[[4-chloro-3-(trifluoromethyl)phenyl]amino]carbonyl]amino]phenoxy]-N-methyl-, NSC-724772, NCGC00167488-01, Sorafenib [USAN:INN:BAN], SR-00000000529, 1uwh, 3gcs, 3heg, 4asd, Hit compound, 8, Sorafenib, 4, 4-(4-(((4-chloro-3-(trifluoromethyl)phenyl)carbamoyl)amino)phenoxy)-N-methylpyridine-2-carboxamide, 4-(4-(3-(4-CHLORO-3-(TRIFLUOROMETHYL)PHENYL)UREIDO)PHENOXY)-N(SUP 2)-METHYLPYRIDINE-2-CARBOXAMIDE, 4-[4-[[[[4-Chloro-3-(trifluoromethyl)phenyl]amino]carbonyl]amino]phenoxy]-N-methyl-2-pyridinecarboxamide; BAY 43-9006; N-[4-Chloro-3-(trifluoromethyl)phenyl]-N'-[4-[2-(N-methylcarbamoyl)-4-pyridyloxy]phenyl]urea; Nevaxar; Sorafenib, Manganese(4+), chloro[[4,4',4'',4'''-(21H,23H-porphine-5,10,15,20-tetrayl-kappaN21,kappaN22,kappaN23,kappaN24)tetrakis[1-methylpyridiniumato]](2-)]-, chloride (1:4), (SP-5-12)-, BAY 439006, Kinome_766, SORAFENIB BASE, SORAFENIB [MI], Sorafenib (USAN/INN), SORAFENIB [USAN], Nexavar (TN) (Bayer), sorafenib tosilate hydrate, SORAFENIB [VANDF], SCHEMBL8218, SORAFENIB [WHO-DD], SORAFENIB [EMA EPAR], BAY 43-9006; Sorafenib, cid_216239, GTPL5711, DTXCID5021128, BDBM16673, L01XE05, BCPP000064, HMS2043A18, HMS3244A15, HMS3244A16, HMS3244B15, HMS3656N20, K00597a, BCP01767, BCP34023, EX-A2894, BAY439006, NSC747971, NSC800934, s7397, STK627350, AKOS005560229, AC-1674, CCG-269400, CS-1590, DB00398, NSC-747971, NSC-800934, PB14443, SB19942, SF-0529, BAY-43-0006, Sorafenib free base (BAY-43-9006), NCGC00167488-02, NCGC00167488-03, NCGC00167488-04, NCGC00167488-05, NCGC00167488-07, NCGC00167488-14, 4(4-{3-[4-Chloro-3-(trifluoromethyl)phenyl]ureido}phenoxy)-N(sup 2)-methylpyridine-2-carboxamide, BS164413, HY-10201, N-(4-chloro-3-(trifluoromethyl)phenyl)-N'-(4-(2-(N-methylcar bamoyl)-4-pyridyloxy)phenyl)urea, SY009239, PA-216239, AM20090614, FT-0650736, FT-0674632, NS00005946, SW202562-4, BA4 43 9006, D08524, EN300-120647, AB00933189-05, AB00933189-06, AB00933189_08, A819449, Q421136, Q-201728, SR-00000000529-1, BRD-K23984367-001-01-8, Z89277543, BAY 439006; BAY439006; BAY-439006, Sorafenib (D3); CM-4307; CM 4307; CM4307;Bay 43-9006 (D3), 4-(4-(3-(4-chloro-3-(trifluoromethyl)phenyl) ureido) phenoxy)-N-methylpicolinamide, 4-(4-(3-(4-chloro-3-(trifluoromethyl)phenyl) ureido)phenoxy)-N-methylpicolinamide, N-(3-trifluoromethyl-4-chlorophenyl)-N'-(4-(2-methylcarbamoyl pyridin-4-yl)oxyphenyl)urea, 4-(4-(3-(4-Chloro-3-(trifluoromethyl)phenyl)ureido)phenoxy)-N(sup 2)- methylpyridine-2-carboxamide, 4-(4-(3-(4-chloro-3-trifluoromethylphenyl)ureido)phenoxy)pyridine-2- carboxyllic acid methyamide-4-methylbenzenesulfonate, 4-(4-{3-[4-chloro-3-(trifluoromethyl)phenyl]ureido}phenoxy)- N-methylpyridine-2-carboxamide, 4-(4-{3-[4-Chloro-3-(trifluoromethyl)phenyl]ureido}phenoxy)-N2-methylpyridine-2-carboxamide, 4-[4-[[4-chloro-3-(trifluoromethyl)phenyl]carbamoylamino]phenoxy]-N-methyl-picolinamide;tosylic acid, 4-{4-[({[4-chloro-3-(trifluoromethyl)phenyl]amino}carbonyl)-amino]phenoxy}-N-methylpyridine-2-carboxamide, 4-{4-[({[4-chloro-3-(trifluoromethyl)phenyl]amino}carbonyl)amino]phenoxy}-N-methyl-pyridine-2-carboxamide, Manganese(4+), chloro[[4,4',4'',4'''-(21H,23H-porphine-5,10,15,20-tetrayl-N21,N22,N23,N24)tetrakis[1-methylpyridiniumato]](2-)]-, chloride (1:4), (SP-5-12)-, N-(4-Chloro-3-(trifluoromethyl)phenyl)-N'-(4-(2-(N-methylcarbamoyl)-4- pyridyloxy)phenyl)urea, N-(4-chloro-3-(trifluoromethyl)phenyl)-N'-(4-(2-(N-methylcarbamoyl)-4-pyridyloxy)phenyl) urea
Drug Type Small molecule
Formula C₂₁H₁₆ClF₃N₄O₃
SMILES CNC(=O)C1=NC=CC(=C1)OC2=CC=C(C=C2)NC(=O)NC3=CC(=C(C=C3)Cl)C(F)(F)F
InChI 1S/C21H16ClF3N4O3/c1-26-19(30)18-11-15(8-9-27-18)32-14-5-2-12(3-6-14)28-20(31)29-13-4-7-17(22)16(10-13)21(23,24)25/h2-11H,1H3,(H,26,30)(H2,28,29,31)
InChIKey MLDQJTXFUGDVEO-UHFFFAOYSA-N
CAS Number 284461-73-0
ChEMBL ID CHEMBL1336
ChEBI ID CHEBI:50924
TTD ID D0W5HK
Drug Bank ID DB00398
KEGG ID D08524
Toxicity Organism Test Type Route(Dose)
rat LD50 intraperitoneal(165 mg/kg)
mouse LD50 intraperitoneal(254 mg/kg)
rat LD50 oral(322 mg/kg)
Structure 2D-img
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2D MOL 3D MOL
03. Combinatorial Therapeutic Effect(s)
Synergistic Effect
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Enhancing Drug Efficacy
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Combination Pair ID: 795
Ref_10
Pair Name Withaferin A, Sorafenib
Partner Name Withaferin A
Disease Info [ICD-11: 2D10.Z] Thyroid cancer Investigative
Biological Phenomena Induction-->Apoptosis
Gene Regulation Down-regulation Phosphorylation CASP3 hsa836
Down-regulation Expression PARP1 hsa142
In Vitro Model B-CPAP Poorly differentiated thyroid gland carcinoma Homo sapiens (Human) CVCL_0153
SW1736 Thyroid gland anaplastic carcinoma Homo sapiens (Human) CVCL_3883
Result Combination therapy with sorafenib + withaferin showed synergistic efficacy in papillary and anaplastic cancers in vitro with significant induction of apoptosis. This combination achieved potent anticancer activity with lower overall doses of sorafenib, indicating a potential strategy to decrease sorafenib toxicity in future translational studies.
Combination Pair ID: 504
Ref_11
Pair Name Usnic acid, Sorafenib
Partner Name Usnic acid
Disease Info [ICD-11: 2C12] Hepatocellular carcinoma Investigative
Biological Phenomena Induction-->Blockade of cell cycle in G0/G1 phase
Gene Regulation Down-regulation Expression MAP2K3 hsa5606
Down-regulation Expression MAPK1 hsa5594
Down-regulation Expression MAPK3 hsa5595
In Vitro Model Hep-G2 Hepatoblastoma Homo sapiens (Human) CVCL_0027
SNU-449 Adult hepatocellular carcinoma Homo sapiens (Human) CVCL_0454
Result Investigation of new treatment option for hepatocellular carcinoma: a combination of sorafenib with usnic acid
Combination Pair ID: 1012
Ref_12
Pair Name Ursolic acid, Sorafenib
Partner Name Ursolic acid
Disease Info [ICD-11: 2C12] Hepatocellular carcinoma Investigative
Biological Phenomena Induction-->Autophagy
Gene Regulation Down-regulation Expression MCL1 hsa4170
In Vitro Model Hep-G2 Hepatoblastoma Homo sapiens (Human) CVCL_0027
SMMC-7721 Human papillomavirus-related cervical adenocarcinoma Homo sapiens (Human) CVCL_0534
Huh-7 Adult hepatocellular carcinoma Homo sapiens (Human) CVCL_0336
H22 Hepatocellular carcinoma Mus musculus (Mouse) CVCL_H613
In Vivo Model To assess the inhibitory effect of different drugs on mouse liver cancer xenografts, six experimental groups of mice were  randomly  set up: (1) Control (saline), (2) UA (4 mg/kg), (3) Sora (4 mg/kg), (4) UA + Sora (UA 4 mg/kg, Sora 4 mg/kg), (5) US NPs (UA 4 mg/kg, Sora 4 mg/kg), (6) US NPs + rapamycin (UA 4 mg/kg, Sora 4 mg/kg), 6 mice in each group.
Result The carrier-free US NPs provide new strategies for HCC treatment and new ideas for the development of novel nano-drug delivery systems containing UA and Sora.
Combination Pair ID: 189
Ref_13
Pair Name Ursolic acid, Sorafenib
Partner Name Ursolic acid
Disease Info [ICD-11: 2A00-2F9Z] Solid tumour or cancer Investigative
Biological Phenomena Induction-->Ferroptosis
Gene Regulation Up-regulation Expression BIM hsa10018
Up-regulation Expression CASP3 hsa836
Up-regulation Expression CASP8 hsa841
Up-regulation Expression CASP9 hsa842
Down-regulation Expression MCL1 hsa4170
Up-regulation Expression PARP1 hsa142
Up-regulation Expression ROS1 hsa6098
Down-regulation Expression SLC7A11 hsa23657
In Vitro Model HCT 116 Colon carcinoma Homo sapiens (Human) CVCL_0291
AGS Gastric adenocarcinoma Homo sapiens (Human) CVCL_0139
In Vivo Model HCT 116 cells (3×10⁶), HCT116 Vector cells (3×10⁶), HCT116 Mcl-1 overexpression cells (3×10⁶) and HCT116 SLC7A11 overexpression cells (3×10⁶) suspended in 0.2 ml of PBS were subcutaneously inoculated into the right flank of each mouse.
Result These results suggest that the synergistic antitumor effects of sorafenib combined with ursolic acid may involve the induction of Mcl-1-related apoptosis and SLC7A11-dependent ferroptosis. Our findings may offer a novel effective therapeutic strategy for tumor treatment.
Combination Pair ID: 350
Ref_14
Pair Name Ursodiol, Sorafenib
Partner Name Ursodiol
Disease Info [ICD-11: 2C12] Hepatocellular carcinoma Investigative
Biological Phenomena Induction-->Apoptosis
Gene Regulation Up-regulation Phosphorylation MAPK1 hsa5594
Down-regulation Phosphorylation STAT3 hsa6774
In Vitro Model Hep-G2 Hepatoblastoma Homo sapiens (Human) CVCL_0027
Result The present findings may represent a promising therapeutic strategy for patients with advanced hepatocellular carcinoma.
Combination Pair ID: 483
Ref_15
Pair Name Tiliroside, Sorafenib
Partner Name Tiliroside
Disease Info [ICD-11: 2C12] Hepatocellular carcinoma Investigative
Biological Phenomena Induction-->Ferroptosis
Gene Regulation Down-regulation Expression FTH1 hsa2495
Down-regulation Expression G6PD hsa2539
Down-regulation Expression GPX4 hsa2879
Up-regulation Expression KEAP1 hsa9817
Down-regulation Expression NFE2L2 hsa4780
Up-regulation Expression SQSTM1 hsa8878
Down-regulation Phosphorylation TBK1 hsa29110
In Vitro Model Hep-G2 Hepatoblastoma Homo sapiens (Human) CVCL_0027
In Vivo Model A total of 2.5×10⁶ HepG2-luciferase cells/100 µl were injected into the left axilla of mice.
Result Our findings imply that tiliroside is a potent TBK1 inhibitor and a candidate natural anti-cancer product that could function as a sensitizer of sorafenib in HCC treatment by targeting TBK1 to induce ferroptosis.
Combination Pair ID: 16
Ref_16
Pair Name Tetrandrine, Sorafenib
Partner Name Tetrandrine
Disease Info [ICD-11: 2C12] Hepatocellular carcinoma Investigative
Biological Phenomena Induction-->Apoptosis
Gene Regulation Down-regulation Phosphorylation AKT1 hsa207
Up-regulation Expression BAX hsa581
Up-regulation Expression BBC3 hsa27113
Down-regulation Expression BCL2 hsa596
Up-regulation Expression BCL2L11 KEGG ID N.A.
Down-regulation Expression BCL-xL hsa598
Down-regulation Expression BID hsa637
Up-regulation Expression CASP3 hsa836
Up-regulation Expression CASP8 hsa841
Up-regulation Expression CASP9 hsa842
Up-regulation Expression CYCS hsa54205
Down-regulation Expression MCL1 hsa4170
Up-regulation Cleavage PARP1 hsa142
In Vitro Model BEL-7402 Human papillomavirus-related cervical adenocarcinoma Homo sapiens (Human) CVCL_5492
HCT 116 Colon carcinoma Homo sapiens (Human) CVCL_0291
In Vivo Model All qualified mice were injected in the right flank with 2×10⁷ HCT116 cells suspended in 0.2 ml of PBS.
Result The antitumour activity of sorafenib plus tetrandrine may be attributed to the induction of the intrinsic apoptosis pathway through ROS/Akt signaling. This finding provides a novel approach that may broaden the clinical application of sorafenib.
Combination Pair ID: 732
Ref_17
Pair Name Tanshinone IIA, Sorafenib
Partner Name Tanshinone IIA
Disease Info [ICD-11: 2C12] Hepatocellular carcinoma Investigative
Biological Phenomena Inhibition-->Epithelial-mesenchymal transition
Gene Regulation Down-regulation Phosphorylation STAT3 hsa6774
In Vitro Model Huh-7 Adult hepatocellular carcinoma Homo sapiens (Human) CVCL_0336
Hep-G2 Hepatoblastoma Homo sapiens (Human) CVCL_0027
MCF-7 Invasive breast carcinoma of no special type Homo sapiens (Human) CVCL_0031
Result A combination therapy using Tan-IIA and sorafenib or SC-1 could be a promising approach to target HCC, and further preclinical investigations are warranted to establish their synergetic advantage.
Combination Pair ID: 46
Ref_18
Pair Name Solamargine, Sorafenib
Partner Name Solamargine
Disease Info [ICD-11: 2C12] Hepatocellular carcinoma Investigative
Gene Regulation Down-regulation Expression HOTTIP KEGG ID N.A.
Up-regulation Expression microRNA 4726 hsa100616153
Down-regulation Expression MUC1 hsa4582
Down-regulation Expression TUG1 hsa55000
In Vitro Model Hep-G2 Hepatoblastoma Homo sapiens (Human) CVCL_0027
Huh-7 Adult hepatocellular carcinoma Homo sapiens (Human) CVCL_0336
Result Our study revealed that SM inhibited the growth of HCC and enhanced the anticancer effect of SF through HOTTIP-TUG1/miR-4726-5p/MUC1 signaling pathway. These findings will provide potential therapeutic targets and strategies for the treatment of HCC.
Combination Pair ID: 99
Ref_19
Pair Name Silibinin, Sorafenib
Partner Name Silibinin
Disease Info [ICD-11: 2C12] Hepatocellular carcinoma Investigative
Biological Phenomena Induction-->Apoptosis
Gene Regulation Down-regulation Phosphorylation AKT1 hsa207
Down-regulation Expression BCL2 hsa596
Up-regulation Cleavage CASP3 hsa836
Down-regulation Expression KLF4 hsa9314
Down-regulation Phosphorylation MAPK1 hsa5594
Down-regulation Phosphorylation MAPK14 hsa1432
Down-regulation Expression MCL1 hsa4170
Down-regulation Expression NANOG hsa79923
Up-regulation Cleavage PARP1 hsa142
Down-regulation Phosphorylation STAT3 hsa6774
In Vitro Model BEL-7404 Human papillomavirus-related cervical adenocarcinoma Homo sapiens (Human) CVCL_6568
Result These results suggested that silibinin improved the efficacy of sorafenib in HCC therapy, indicating a clinical promising therapeutic strategy for HCC patients.
Combination Pair ID: 210
Ref_20
Pair Name Rhizoma Paridis saponins, Sorafenib
Partner Name Rhizoma Paridis saponins
Disease Info [ICD-11: 2C12] Hepatocellular carcinoma Investigative
Biological Phenomena Inhibition-->Glycolysis
Gene Regulation Down-regulation Expression AKT1 hsa207
Down-regulation Expression CPT1A hsa1374
Down-regulation Expression CPT1A hsa1374
Up-regulation Activity DUOX2 hsa50506
Down-regulation Expression FASN hsa2194
Down-regulation Expression HIF1A hsa3091
Down-regulation Expression LDHA hsa3939
Down-regulation Phosphorylation MTOR hsa2475
Down-regulation Expression MYC hsa4609
Down-regulation Phosphorylation PIK3CA hsa5290
Up-regulation Activity SDHB hsa6390
Down-regulation Expression SLC2A1 hsa6513
Up-regulation Expression TP53 hsa7157
In Vivo Model 5×10⁶ of H22 tumor cells were subcutaneously subaxillary inoculated in 24 mice.
Result All of that provided possibility to overcome the intolerance of sorafenib by drug compatibility through protection against mitochondria damage, inhibition of anaerobic glycolysis and suppression of lipid synthesis based on PI3K/Akt/mTOR pathway.
Combination Pair ID: 812
Ref_21
Pair Name Resveratrol, Sorafenib
Partner Name Resveratrol
Disease Info [ICD-11: 2C90.0] Renal cell carcinoma Investigative
Gene Regulation Down-regulation Phosphorylation AKT1 hsa207
Up-regulation Expression BAX hsa581
Down-regulation Expression BCL2 hsa596
Down-regulation Expression HIF1A hsa3091
Down-regulation Phosphorylation MAPK1 hsa5594
Down-regulation Phosphorylation MEK1 hsa5604
Down-regulation Phosphorylation MTOR hsa2475
Down-regulation Phosphorylation RAF1 hsa5894
Down-regulation Phosphorylation RPS6KB1 hsa6198
Down-regulation Expression VEGFA hsa7422
In Vitro Model RenCa Mouse kidney carcinoma Mus musculus (Mouse) CVCL_2174
HEK293T Healthy Homo sapiens (Human) CVCL_0063
In Vivo Model After reaching the required number of cells, the cells were harvested, washed and appropriate amount of PBS was added to prepare Renca cell suspension at a concentration of 5×10⁷ cells/mL. 0.2 mL was injected into the armpit of each mouse, and weighed and grouped the next day.
Result PEGylated resveratrol combined with sorafenib can achieve synergistic anti-RCC activity, and the mechanism may be related to the inhibition of Akt/mTOR/p70S6k-4EBP-1 and c-Raf7MEK/ERK signaling pathways.
Combination Pair ID: 804
Ref_22
Pair Name Pterostilbene, Sorafenib
Partner Name Pterostilbene
Disease Info [ICD-11: 2B72] Gastric cancer Investigative
Biological Phenomena Induction-->Autophagy
Gene Regulation Down-regulation Expression BCL2 hsa596
Up-regulation Cleavage CASP3 hsa836
Up-regulation Cleavage CASP9 hsa842
Down-regulation Expression CCND1 hsa595
Down-regulation Expression CDK2 hsa1017
Down-regulation Expression CDK4 hsa1019
Down-regulation Expression CDK6 hsa1021
Up-regulation Expression MAP1LC3A hsa84557
Up-regulation Cleavage PARP1 hsa142
Down-regulation Expression SQSTM1 hsa8878
In Vitro Model NCI-N87 Gastric tubular adenocarcinoma Homo sapiens (Human) CVCL_1603
MKN45 Gastric adenocarcinoma Homo sapiens (Human) CVCL_0434
In Vivo Model N87 cells (3×10⁵ cells) were suspended in 0.1 mL of PBS and inoculated subcutaneously into the right flank of five-week-old male BALB/c nude mice
Result PET obviously enhanced sorafenib's antitumour effects against GAC through inhibiting cell proliferation, inducing autophagy and promoting apoptosis. The combination therapy with PET and sorafenib may serve as a novel therapeutic strategy for treating GAC and deserve further clinical trials.
Combination Pair ID: 587
Ref_23
Pair Name Pristimerin, Sorafenib
Partner Name Pristimerin
Disease Info [ICD-11: 2C12] Hepatocellular carcinoma Investigative
Biological Phenomena Inhibition-->Cell migration and angiogenesis
Gene Regulation Down-regulation Phosphorylation AKT1 hsa207
Up-regulation Expression BAX hsa581
Down-regulation Expression BCL2 hsa596
Up-regulation Cleavage CASP3 hsa836
Up-regulation Cleavage CASP4 hsa837
Up-regulation Expression CYCS hsa54205
Up-regulation Expression DDIT3 hsa1649
Up-regulation Phosphorylation EIF2AK3 hsa9451
Up-regulation Phosphorylation EIF2S1 hsa1965
Up-regulation Expression FOXO1 hsa2308
Up-regulation Expression HSPA5 hsa3309
Up-regulation Expression PSMD9 hsa5715
In Vitro Model CRHCs CRHCs isolated from the 9 patients would be used for the following experiments. Homo sapiens (Human) N.A.
Result Pristimerin synergistically sensitizes conditionally reprogrammed patient derived-primary hepatocellular carcinoma cells to sorafenib through endoplasmic reticulum stress and ROS generation by modulating Akt/FoxO1/p27kip1 signaling pathway
Combination Pair ID: 964
Ref_24
Pair Name Platycodin D, Sorafenib
Partner Name Platycodin D
Disease Info [ICD-11: 2C82] Prostate cancer Investigative
Biological Phenomena Inhibition-->Cell proliferation
Gene Regulation Up-regulation Phosphorylation AKT1 hsa207
Up-regulation Expression BIM hsa10018
Up-regulation Cleavage CASP3 hsa836
Down-regulation Expression CCND1 hsa595
Down-regulation Expression CDK4 hsa1019
Down-regulation Expression CDK6 hsa1021
Up-regulation Expression FASLG hsa356
Up-regulation Expression FOXO3 hsa2309
Up-regulation Cleavage PARP1 hsa142
Up-regulation Expression TNFSF10 hsa8743
In Vitro Model PC-3 Prostate carcinoma Homo sapiens (Human) CVCL_0035
DU145 Prostate carcinoma Homo sapiens (Human) CVCL_0105
In Vivo Model PC3 cells (shRNA-FOXO3a cells and MOCK cells) were injected subcutaneously into the left inguinal area of nude mice (BALB/c, nu/nu, male, 6-8 weeks old)
Result The combination of Platycodin D and sorafenib may exert potent anti-cancer effects specifically via FOXO3a
Combination Pair ID: 12
Ref_25
Pair Name Piperlongumine, Sorafenib
Partner Name Piperlongumine
Disease Info [ICD-11: 2C12] Hepatocellular carcinoma Investigative
Biological Phenomena Induction-->Blockade of cell cycle in G2/M phase
Gene Regulation Up-regulation Expression BAX hsa581
Down-regulation Expression BCL2 hsa596
Up-regulation Cleavage CASP3 hsa836
Down-regulation Expression CDK1 hsa983
Down-regulation Expression CPSF7 hsa79869
Down-regulation Expression MKI67 hsa4288
Up-regulation Cleavage PARP1 hsa142
Up-regulation Phosphorylation PRKAA1 hsa5562
In Vitro Model HCCLM3 Adult hepatocellular carcinoma Homo sapiens (Human) CVCL_6832
SMMC-7721 Human papillomavirus-related cervical adenocarcinoma Homo sapiens (Human) CVCL_0534
Result Piperlongumine synergistically enhances the antitumour activity of sorafenib by mediating ROS-AMPK activation and targeting CPSF7 in liver cancer
Combination Pair ID: 194
Ref_26
Pair Name Oleanolic Acid, Sorafenib
Partner Name Oleanolic Acid
Disease Info [ICD-11: 2C12] Hepatocellular carcinoma Investigative
Biological Phenomena Induction-->Oxidative Stress
Gene Regulation Up-regulation Cleavage CASP3 hsa836
Up-regulation Cleavage CASP7 hsa840
Up-regulation Expression ROS1 hsa6098
In Vitro Model Huh-7 Adult hepatocellular carcinoma Homo sapiens (Human) CVCL_0336
Hep-G2 Hepatoblastoma Homo sapiens (Human) CVCL_0027
Result OA represents a novel approach to increase the sensitivity of HCC cells to Sorafenib via oxidative stress.
Combination Pair ID: 642
Ref_27
Pair Name Nobiletin, Sorafenib
Partner Name Nobiletin
Disease Info [ICD-11: 2C82] Prostate cancer Investigative
Biological Phenomena Induction-->Blockade of cell cycle in G0/G1 phase
Gene Regulation Up-regulation Expression BAX hsa581
Up-regulation Expression CDKN1A hsa1026
Up-regulation Expression RB1 hsa5925
In Vitro Model PC-3 Prostate carcinoma Homo sapiens (Human) CVCL_0035
Result NOB and SOR combination was more effective than SOR and NOB alone and reduced the exposure time for SOR and NOB in PC-3 cells. Combination strategy is a therapeutic potential to improve efficacy and reduce side-effect of SOR for the treatment of metastatic prostate cancer cells.
Combination Pair ID: 846
Ref_28
Pair Name Luteolin, Sorafenib
Partner Name Luteolin
Disease Info [ICD-11: 2C12] Hepatocellular carcinoma Investigative
Biological Phenomena Induction-->Apoptosis
Gene Regulation Up-regulation Cleavage CASP3 hsa836
Up-regulation Phosphorylation MAPK8 hsa5599
Up-regulation Cleavage PARP1 hsa142
In Vitro Model Hep 3B2.1-7 Childhood hepatocellular carcinoma Homo sapiens (Human) CVCL_0326
SMMC-7721 Human papillomavirus-related cervical adenocarcinoma Homo sapiens (Human) CVCL_0534
Result Sorafenib and luteolin combination synergistically kills HCC cells through JNK-mediated apoptosis, and luteolin may be an ideal candidate for increasing the activity of sorafenib in HCC therapy.
Combination Pair ID: 96
Ref_29
Pair Name Licochalcone A, Sorafenib
Partner Name Licochalcone A
Disease Info [ICD-11: 2C12] Hepatocellular carcinoma Investigative
Biological Phenomena Inhibition-->Cell metastasis
Gene Regulation Down-regulation Expression MAP2K4 hsa6416
Down-regulation Expression MAPK8 hsa5599
Down-regulation Expression PLAU hsa5328
In Vitro Model SK-HEP-1 Liver and intrahepatic bile duct epithelial neoplasm Homo sapiens (Human) CVCL_0525
Huh-7 Adult hepatocellular carcinoma Homo sapiens (Human) CVCL_0336
Result These findings first revealed the synergistic effects of LicA and Sor cotreatment against human HCC cells, further suggesting that beneficial effects on tumor regression could be confirmed through prospective clinical trials.
Combination Pair ID: 855
Ref_30
Pair Name Kaempferol, Sorafenib
Partner Name Kaempferol
Disease Info [ICD-11: 2C12] Hepatocellular carcinoma Investigative
Gene Regulation Down-regulation Expression ABCB1 hsa5243
In Vitro Model Hep-G2 Hepatoblastoma Homo sapiens (Human) CVCL_0027
Result Kaempferol is able to sensitize the HepG2 and N1S1 against the sub-toxic concentration of sorafenib. Hence, we consider that the efficacy of sorafenib chemotherapy can be enhanced by the significant approach of combining the sub-toxic concentrations of sorafenib with kaempferol. Thus, kaempferol can be used as a better candidate molecule along with sorafenib for enhancing its efficacy, if validated through preclinical studies.
Combination Pair ID: 204
Ref_31
Pair Name Ginsenoside Rg3, Sorafenib
Partner Name Ginsenoside Rg3
Disease Info [ICD-11: 2C12] Hepatocellular carcinoma Investigative
Biological Phenomena Induction-->Apoptosis
Gene Regulation Down-regulation Phosphorylation AKT1 hsa207
Up-regulation Expression BAX hsa581
Up-regulation Cleavage CASP3 hsa836
Down-regulation Phosphorylation PDK1 hsa5163
Up-regulation Expression PTEN hsa5728
In Vitro Model Hep-G2 Hepatoblastoma Homo sapiens (Human) CVCL_0027
Huh-7 Adult hepatocellular carcinoma Homo sapiens (Human) CVCL_0336
In Vivo Model Huh7 cells (1×10⁶) in 100 μL PBS were injected subcutaneously into the flank of nude mice. Mice (N = 5 of each group) were randomly divided into four groups once the tumor volume reached 0.2 cm*3.
Result These findings suggest a promising strategy for HCC treatment, which could be performed in a sufficiently frequent manner.
Combination Pair ID: 203
Ref_32
Pair Name Ginsenoside Rg3, Sorafenib
Partner Name Ginsenoside Rg3
Disease Info [ICD-11: 2C12] Hepatocellular carcinoma Investigative
Biological Phenomena Inhibition-->Glycolysis
Gene Regulation Down-regulation Expression AKT1 hsa207
Down-regulation Expression HK2 hsa3099
Down-regulation Expression PIK3CA hsa5290
In Vitro Model Hep-G2 Hepatoblastoma Homo sapiens (Human) CVCL_0027
BEL-7404 Human papillomavirus-related cervical adenocarcinoma Homo sapiens (Human) CVCL_6568
Result Rg3 has a synergistic effect on the sensitivity of HepG2 and Bel7404 hepatoma cells to SFN, which is related to HK2-mediated glycolysis and the PI3K/Akt signaling pathway.
Combination Pair ID: 632
Ref_33
Pair Name Fisetin, Sorafenib
Partner Name Fisetin
Disease Info [ICD-11: 2C30] Melanoma Investigative
Biological Phenomena Inhibition-->Epithelial-mesenchymal transition
Gene Regulation Up-regulation Expression CDH1 hsa999
Down-regulation Expression CDH2 hsa1000
Down-regulation Expression FN1 hsa2335
Down-regulation Expression MMP2 hsa4313
Down-regulation Expression MMP9 hsa4318
Down-regulation Expression SNAI1 hsa6615
Down-regulation Expression SNAI2 hsa6591
Down-regulation Expression TWIST1 hsa7291
Down-regulation Expression VIM hsa7431
Down-regulation Expression ZEB1 hsa6935
In Vitro Model A-375 Amelanotic melanoma Homo sapiens (Human) CVCL_0132
SK-MEL-28 Cutaneous melanoma Homo sapiens (Human) CVCL_0526
In Vivo Model Female athymic nude mice of five weeks age were subcutaneously transplanted with A375 or SK-MEL-28 cells (2.5×10⁶ A375 cells in 50 ul DMEM + 50 ul matrigel or 5×10⁶ SK-MEL-28 cells in 50 ul RPMI + 50 ul matrigel) in each flank
Result Our findings demonstrate that fisetin potentiates the anti-invasive and anti-metastatic effects of sorafenib. Our data suggest that fisetin may be a worthy adjuvant chemotherapy for the management of melanoma.
Combination Pair ID: 633
Ref_34
Pair Name Fisetin, Sorafenib
Partner Name Fisetin
Disease Info [ICD-11: 2C77] Cervical cancer Investigative
Biological Phenomena Induction-->Mitochondria-mediated apoptosis
Gene Regulation Up-regulation Expression BAX hsa581
Up-regulation Expression BCL2 hsa596
Up-regulation Expression CASP3 hsa836
Up-regulation Expression CASP8 hsa841
Up-regulation Expression PARP1 hsa142
Up-regulation Expression TNFRSF10B hsa8795
In Vitro Model HeLa Human papillomavirus-related cervical adenocarcinoma Homo sapiens (Human) CVCL_0030
In Vivo Model For the in vivo experiments, 1×10⁶ HeLa cells (diluted in Matrigel) were established by subcutaneous injec tion into the animal's right flank.
Result The combination of fisetin and sorafenib exerted better synergistic effects in vitro and in vivo than either agent used alone against human cervical cancer, and this synergism was based on apoptotic potential through a mitochondrial- and DR5-dependent caspase-8/caspase-3 signaling pathway
Combination Pair ID: 634
Ref_35
Pair Name Fisetin, Sorafenib
Partner Name Fisetin
Disease Info [ICD-11: 2C30] Melanoma Investigative
Biological Phenomena Induction-->Apoptosis
Gene Regulation Down-regulation Expression AKT1 hsa207
Up-regulation Expression BAK1 hsa578
Up-regulation Expression BAX hsa581
Down-regulation Expression BCL2 hsa596
Up-regulation Expression CASP3 hsa836
Down-regulation Phosphorylation MAP2K2 hsa5605
Down-regulation Expression MAPK3 hsa5595
Down-regulation Expression MCL1 hsa4170
Down-regulation Phosphorylation MEK1 hsa5604
Down-regulation Expression MTOR hsa2475
Up-regulation Expression PARP1 hsa142
Down-regulation Expression PIK3CA hsa5290
In Vitro Model RPMI-7951 Melanoma Homo sapiens (Human) CVCL_1666
A-375 Amelanotic melanoma Homo sapiens (Human) CVCL_0132
In Vivo Model Mice were subcutaneously inoculated with 0.1ml of 2.5×10⁶ A375 cells or 5×10*6 SK-MEL-28 cells (prepared in a 50ul media + 50ul matrigel) in each flank to initiate tumor growth.
Result Fisetin potentiates sorafenib-induced apoptosis and abrogates tumor growth in athymic nude mice implanted with BRAF-mutated melanoma cells.
Combination Pair ID: 943
Ref_36
Pair Name Escin, Sorafenib
Partner Name Escin
Disease Info [ICD-11: 2C12] Hepatocellular carcinoma Investigative
Biological Phenomena Induction-->Blockade of cell cycle in G0/G1 phase
Gene Regulation Up-regulation Expression BECN1 hsa8678
Up-regulation Expression MAP1LC3B hsa81631
Up-regulation Expression SQSTM1 hsa8878
In Vitro Model Hep-G2 Hepatoblastoma Homo sapiens (Human) CVCL_0027
In Vivo Model For the following 4 weeks, the animalsreceived daily treatments of water/saline as vehicle, sorafenib (10 mg/kgbw, oral) and escin (10 mg/kg bw, i.p.) alone and also in combination.
Result Escin and sorafenib combination potentially up-regulates p62 to block autophagy to induce late apoptosis in liver cancer cells.
Combination Pair ID: 165
Ref_37
Pair Name Dihydroartemisinin, Sorafenib
Partner Name Dihydroartemisinin
Disease Info [ICD-11: 2C12] Hepatocellular carcinoma Investigative
Biological Phenomena Induction-->Ferroptosis
Gene Regulation Down-regulation Expression GCLC hsa2729
Down-regulation Expression GPX4 hsa2879
Down-regulation Expression GSS hsa2937
Down-regulation Expression HMOX1 hsa3162
Up-regulation Expression ROS1 hsa6098
Down-regulation Expression SLC7A11 hsa23657
Up-regulation Expression SMG1 hsa23049
In Vitro Model Hep-G2 Hepatoblastoma Homo sapiens (Human) CVCL_0027
SW480 Colon adenocarcinoma Homo sapiens (Human) CVCL_0546
In Vivo Model 5×10⁶ of HepG2 cells were injected into the right flank of 6-week-old athymic female mice (Balb/c nude mice).
Result DHA and Sora had the same mechanism, and the combined application of them could have a synergistic anti-tumor effect by inducing ferroptosis and inhibiting energy metabolism in HepG2 cells.
Combination Pair ID: 53
Ref_38
Pair Name Daurinoline, Sorafenib
Partner Name Daurinoline
Disease Info [ICD-11: 2C12] Hepatocellular carcinoma Investigative
Biological Phenomena Inhibition-->Vasculogenic mimicry
Gene Regulation Down-regulation Phosphorylation AKT1 hsa207
Up-regulation Expression BAX hsa581
Down-regulation Expression BCL2 hsa596
Up-regulation Cleavage CASP3 hsa836
Up-regulation Cleavage CASP9 hsa842
Down-regulation Expression CCND1 hsa595
Down-regulation Expression CCNE1 hsa898
Down-regulation Expression CDK2 hsa1017
Down-regulation Expression CDK4 hsa1019
Up-regulation Expression CDKN1A hsa1026
Down-regulation Expression KDR hsa3791
Down-regulation Phosphorylation MAPK1 hsa5594
Down-regulation Phosphorylation MAPK3 hsa5595
Up-regulation Cleavage PARP1 hsa142
Up-regulation Expression PSMD9 hsa5715
Down-regulation Activity RHOA hsa387
Down-regulation Activity ROCK2 hsa9475
In Vitro Model QGY-7703 Human papillomavirus-related cervical adenocarcinoma Homo sapiens (Human) CVCL_6715
MHCC97-H Adult hepatocellular carcinoma Homo sapiens (Human) CVCL_4972
In Vivo Model MHCC-97H cells were suspended in cold PBS at a density of 1×10⁷ cells/ml, and 100 μl of the cell suspension was subcutaneously injected into the right flank of each mouse.
Result Our study provides insights into the molecular mechanisms underlying DS-induced inhibition of VM, which may facilitate the development of a novel clinical anti-HCC drug. Moreover, our findings suggest that the combination of DS and sorafenib constitutes a potential therapeutic strategy for HCC.
Combination Pair ID: 219
Ref_39
Pair Name Cucurbitacin B, Sorafenib
Partner Name Cucurbitacin B
Disease Info [ICD-11: 2C12] Hepatocellular carcinoma Investigative
Gene Regulation Up-regulation Cleavage CASP3 hsa836
Up-regulation Cleavage CASP9 hsa842
Down-regulation Phosphorylation STAT3 hsa6774
In Vitro Model Hep-G2 Hepatoblastoma Homo sapiens (Human) CVCL_0027
In Vivo Model 5×10⁶ HepG2 cells were injected subcutaneously into the right flank of nude mice.
Result Sorafenib and CuB exert synergistic antitumor effects through a pathway that may involve STAT3 phosphorylation, and this may represent a promising therapeutic approach for treatment of HCC.
Combination Pair ID: 739
Ref_40
Pair Name Crocin, Sorafenib
Partner Name Crocin
Disease Info [ICD-11: 2C12] Hepatocellular carcinoma Investigative
Biological Phenomena Induction-->Apoptosis
Gene Regulation Up-regulation Expression BAX hsa581
Down-regulation Expression BCL2 hsa596
Down-regulation Expression COX2 hsa4513
Down-regulation Expression PARP1 hsa142
Down-regulation Expression PCNA hsa5111
Down-regulation Expression RELA hsa5970
In Vivo Model Diethylnitrosamine was administered intraperitoneally to rats once a week for 15 weeks, leading to cirrhosis, and then 19 weeks later, leading to multifocal HCC. After 16 weeks of cancer induction, CR (200 mg/kg daily) and SB (10 mg/kg daily) were given orally to rats for three weeks, either separately or in combination.
Result CR potentiates the suppressive effects of SB on tumor growth and provides the opportunity to strengthen the therapeutic effects of SB in the treatment of HCC.
Combination Pair ID: 834
Ref_41
Pair Name Capsaicin, Sorafenib
Partner Name Capsaicin
Disease Info [ICD-11: 2C12] Hepatocellular carcinoma Investigative
Biological Phenomena Induction-->Autophagy
Gene Regulation Up-regulation Expression BAX hsa581
Down-regulation Expression BCL2 hsa596
Up-regulation Expression CASP3 hsa836
Down-regulation Expression EGFR hsa1956
Up-regulation Expression PARP1 hsa142
In Vitro Model LM3 Malignant neoplasms of the mouse mammary gland Mus musculus (Mouse) CVCL_D269
Hep 3B2.1-7 Childhood hepatocellular carcinoma Homo sapiens (Human) CVCL_0326
Huh-7 Adult hepatocellular carcinoma Homo sapiens (Human) CVCL_0336
In Vivo Model Five-week-old BALB/C nude mice received a subcutaneous injection of 1×10⁷ LM3 cells suspended in 100 uL sterile PBS into the right flank.
Result These data confirm that capsaicin and sorafenib combination treatment inhibits the growth, invasion and metastasis of HCC cells and induces autophagy in a synergistic manner, supporting its potential as a therapeutic option for HCC.
Combination Pair ID: 1
Ref_42
Pair Name Camptothecin, Sorafenib
Partner Name Camptothecin
Disease Info [ICD-11: 2C12] Hepatocellular carcinoma Investigative
Biological Phenomena Induction-->Ferroptosis
Gene Regulation Down-regulation Expression ABCG2 hsa9429
Down-regulation Expression MT1G hsa4495
Down-regulation Expression NFE2L2 hsa4780
Down-regulation Expression SLC7A11 hsa23657
Down-regulation Expression SQSTM1 hsa8878
In Vitro Model Hep-G2 Hepatoblastoma Homo sapiens (Human) CVCL_0027
Huh-7 Adult hepatocellular carcinoma Homo sapiens (Human) CVCL_0336
Result The synergetic combination significantly increases lipid peroxidation and iron concentration, decreases TAC, GPX4 and GR activity, and reduces the expression of both Nrf2 and SLC7A11. The downregulation of Nrf2 expression has a vital role in the reduction of resistance mediators to sorafenib against HCC cells like (p62, MT1G, and ABCG2) and improves the cellular uptake of sorafenib. The current study provided evidence that Nrf2 inhibition by CPT improves sorafenib's sensitivity and reduces sorafenib's resistance via the augmentation of sorafenib's ferroptosis action.
Combination Pair ID: 354
Ref_43
Pair Name Bufalin, Sorafenib
Partner Name Bufalin
Disease Info [ICD-11: 2C12] Hepatocellular carcinoma Investigative
Biological Phenomena Induction-->Tumor vascular microenvironment
Gene Regulation Down-regulation Phosphorylation MTOR hsa2475
Down-regulation Expression VEGFA hsa7422
In Vitro Model PLC/PRF/5 Adult hepatocellular carcinoma Homo sapiens (Human) CVCL_0485
SMMC-7721 Human papillomavirus-related cervical adenocarcinoma Homo sapiens (Human) CVCL_0534
In Vivo Model A total of 5×10⁶ SMMC-7721 cells in 0.2 ml phosphate-buffered saline (PBS) were injected into the right flank of each mouse to form subcutaneous tumors.
Result The results revealed a synergistic anti-hepatoma effect of bufalin combined with sorafenib via affecting the tumor vascular microenvironment by targeting mTOR/VEGF signaling.
Combination Pair ID: 351
Ref_44
Pair Name Bufalin, Sorafenib
Partner Name Bufalin
Disease Info [ICD-11: 2C25] Lung cancer Investigative
Biological Phenomena Induction-->Apoptosis
Gene Regulation Up-regulation Expression APAF1 hsa317
Up-regulation Expression BAD hsa572
Up-regulation Expression BAX hsa581
Down-regulation Expression BCL2 hsa596
Up-regulation Expression CASP3 hsa836
Up-regulation Expression CASP9 hsa842
Down-regulation Expression CAT hsa847
Up-regulation Expression SOD1 hsa6647
In Vitro Model NCI-H292 Lung mucoepidermoid carcinoma Homo sapiens (Human) CVCL_0455
Result Sorafenib in combination with bufalin shows more potent cytotoxic effects and cell apoptosis than sorafenib or bufalin treatment alone in NCI-H292 cells. The combined treatment significantly enhanced apoptotic cell death in NCI-H292 lung cancer cells by activating ROS-, mitochondria-, and caspase-signaling pathways in vitro.
Combination Pair ID: 679
Ref_45
Pair Name Betulinic Acid, Sorafenib
Partner Name Betulinic Acid
Disease Info [ICD-11: 2C10] Pancreatic cancer Investigative
Biological Phenomena Induction-->Blockade of cell cycle in G2/M phase
Gene Regulation Down-regulation Phosphorylation AKT1 hsa207
Down-regulation Expression CCND1 hsa595
Up-regulation Expression CDKN1A hsa1026
Down-regulation Expression MYC hsa4609
In Vitro Model AsPC-1 Pancreatic ductal adenocarcinoma Homo sapiens (Human) CVCL_0152
BxPC-3 Pancreatic ductal adenocarcinoma Homo sapiens (Human) CVCL_0186
Capan-1 Pancreatic ductal adenocarcinoma Homo sapiens (Human) CVCL_0237
Result We showed that combined treatment with low concentrations of sorafenib and betulinic acid had the capacity to inhibit proliferation and abolish clonogenic activity in PDAC cell lines.
Combination Pair ID: 678
Ref_46
Pair Name Betulinic Acid, Sorafenib
Partner Name Betulinic Acid
Disease Info [ICD-11: 2C25] Lung cancer Investigative
Biological Phenomena Induction-->Apoptosis
Gene Regulation Down-regulation Expression AKT1 hsa207
Up-regulation Expression BAX hsa581
Down-regulation Expression BCL2 hsa596
Down-regulation Expression BCL-xL hsa598
Up-regulation Expression DDIT3 hsa1649
Down-regulation Expression MTOR hsa2475
In Vitro Model A-549 Lung adenocarcinoma Homo sapiens (Human) CVCL_0023
NCI-H358 Minimally invasive lung adenocarcinoma Homo sapiens (Human) CVCL_1559
A-427 Lung adenocarcinoma Homo sapiens (Human) CVCL_1055
Result We showed that combination therapy with low concentrations of sorafenib and betulinic acid had the capacity to induce high levels of cell death and abolish clonogenic activity in some NSCLC cell lines regardless of KRAS mutations.
Combination Pair ID: 688
Ref_47
Pair Name Betulin, Sorafenib
Partner Name Betulin
Disease Info [ICD-11: 2C12] Hepatocellular carcinoma Investigative
Biological Phenomena Inhibition-->Glycolysis
Gene Regulation Up-regulation Expression SREBF1 hsa6720
In Vitro Model Hep-G2 Hepatoblastoma Homo sapiens (Human) CVCL_0027
Huh-7 Adult hepatocellular carcinoma Homo sapiens (Human) CVCL_0336
SMMC-7721 Human papillomavirus-related cervical adenocarcinoma Homo sapiens (Human) CVCL_0534
BEL-7402 Human papillomavirus-related cervical adenocarcinoma Homo sapiens (Human) CVCL_5492
MHCC97-L Adult hepatocellular carcinoma Homo sapiens (Human) CVCL_4973
MHCC97-H Adult hepatocellular carcinoma Homo sapiens (Human) CVCL_4972
In Vivo Model HCC cells were cultured, and the cells were injected subcutaneously into nude mice, antitumor agents were intragastrically administered 2–3 days after injection of HCC cells.
Result Our data show that SREBP-1 inhibition facilitated the antitumor effects of Sorafenib on HCC cells and xenograft tumors.
Combination Pair ID: 529
Ref_48
Pair Name Beta-Ionone, Sorafenib
Partner Name Beta-Ionone
Disease Info [ICD-11: 2C12] Hepatocellular carcinoma Investigative
Biological Phenomena Inhibition-->Cell migration
Gene Regulation Down-regulation Expression MMP2 hsa4313
Down-regulation Expression MMP9 hsa4318
Down-regulation Expression PTK2 hsa5747
Down-regulation Expression RAC1 hsa5879
Down-regulation Expression RHO hsa6010
Up-regulation Expression TIMP1 hsa7076
Up-regulation Expression TIMP2 hsa7077
In Vitro Model SK-HEP-1 Liver and intrahepatic bile duct epithelial neoplasm Homo sapiens (Human) CVCL_0525
Result SF enhanced the suppressing effect of BI (1-50 μM) on the viability of SK-Hep-1 cells, but not on murine hepatic BNL CL.2 cells, indicating the selective cytotoxicity of this combination on tumor cells. The combination of SF and BI could be a potential therapeutic strategy against human hepatoma cells.
Combination Pair ID: 30
Ref_49
Pair Name Berbamine, Sorafenib
Partner Name Berbamine
Disease Info [ICD-11: 2C12] Hepatocellular carcinoma Investigative
Biological Phenomena Target-->Na(+)/K(+)-ATPase
Gene Regulation Up-regulation Cleavage CASP3 hsa836
Down-regulation Expression CCND1 hsa595
Up-regulation Phosphorylation EGFR hsa1956
Up-regulation Phosphorylation IGF1R hsa3480
Up-regulation Phosphorylation MAPK1 hsa5594
Up-regulation Phosphorylation MAPK14 hsa1432
Down-regulation Expression MCL1 hsa4170
Down-regulation Expression MYC hsa4609
Up-regulation Cleavage PARP1 hsa142
Up-regulation Phosphorylation SRC hsa6714
In Vitro Model Hep-G2 Hepatoblastoma Homo sapiens (Human) CVCL_0027
SK-HEP-1 Liver and intrahepatic bile duct epithelial neoplasm Homo sapiens (Human) CVCL_0525
In Vivo Model 5×10⁶ HepG2 cells in 200 μl PBS were subcutaneously injected into the mice at 6 weeks of age.
Result Targeting Na+/K+-ATPase by berbamine and ouabain synergizes with sorafenib to inhibit hepatocellular carcinoma
Combination Pair ID: 29
Ref_50
Pair Name Berbamine, Sorafenib
Partner Name Berbamine
Disease Info [ICD-11: 2C12] Hepatocellular carcinoma Investigative
Biological Phenomena Induction-->Apoptosis
Gene Regulation Down-regulation Expression BCL2 hsa596
Up-regulation Cleavage CASP3 hsa836
Down-regulation Expression CCND1 hsa595
Down-regulation Expression CDK4 hsa1019
Down-regulation Expression CDK6 hsa1021
Up-regulation Cleavage PARP1 hsa142
Down-regulation Phosphorylation RB1 hsa5925
Down-regulation Phosphorylation STAT3 hsa6774
In Vitro Model HCCLM3 Adult hepatocellular carcinoma Homo sapiens (Human) CVCL_6832
L-02 Papillomavirus-related cervical adenocarcinoma Homo sapiens (Human) CVCL_6926
Result These findings identify a new type of natural STAT3 inhibitor and provide a novel approach to the enhancement of SORA efficacy by blocking the activation of STAT3.
Combination Pair ID: 1015
Ref_51
Pair Name Astaxanthin, Sorafenib
Partner Name Astaxanthin
Disease Info [ICD-11: 2C12] Hepatocellular carcinoma Investigative
Biological Phenomena Inhibition-->Tumor angiogenesis
Gene Regulation Up-regulation Expression BAX hsa581
Down-regulation Expression BCL2 hsa596
Down-regulation Expression BNIP3 hsa664
Down-regulation Expression EGLN1 hsa54583
Up-regulation Expression HIF1A hsa3091
Down-regulation Phosphorylation JAK2 hsa3717
Down-regulation Phosphorylation STAT3 hsa6774
Down-regulation Expression VEGFA hsa7422
Up-regulation Phosphorylation VHL hsa7428
In Vivo Model This experiment was performed using the H22 tumor-bearing mousemodel and the Hepa1-6 tumor-bearing mouse model.
Result Astaxanthin Augmented the Anti-Hepatocellular Carcinoma Efficacy of Sorafenib Through the Inhibition of the JAK2/STAT3 Signaling Pathway and Mitigation of Hypoxia within the Tumor Microenvironment
Combination Pair ID: 169
Ref_52
Pair Name Artesunate, Sorafenib
Partner Name Artesunate
Disease Info [ICD-11: 2C12] Hepatocellular carcinoma Investigative
Gene Regulation Down-regulation Expression NUS1 hsa116150
In Vitro Model Hep-G2 Hepatoblastoma Homo sapiens (Human) CVCL_0027
Result We report that sorafenib treatment in combination with artesunate overcomes HCC resistance to sorafenib alone in a cell culture model.
Combination Pair ID: 1006
Ref_53
Pair Name Artesunate, Sorafenib
Partner Name Artesunate
Disease Info [ICD-11: XH50P3] Non‑hodgkin lymphoma Investigative
Biological Phenomena Induction-->Ferroptosis
Gene Regulation Up-regulation Cleavage CASP3 hsa836
Down-regulation Expression GPX4 hsa2879
Down-regulation Expression MCL1 hsa4170
Up-regulation Cleavage PARP1 hsa142
Down-regulation Expression PECAM1 hsa5175
Down-regulation Expression STAT3 hsa6774
In Vitro Model SU-DHL-4 Diffuse large B-cell lymphoma Homo sapiens (Human) CVCL_0539
Result Artesunate synergistically promotes sorafenib‑induced apoptosis and ferroptosis in non‑Hodgkin lymphoma cells through inhibition of the STAT3 pathway
Combination Pair ID: 1005
Ref_54
Pair Name Artesunate, Sorafenib
Partner Name Artesunate
Disease Info [ICD-11: 2C12] Hepatocellular carcinoma Investigative
Biological Phenomena Induction-->Mitochondria-dependent autophagy
Gene Regulation Down-regulation Expression AFAP1L2 hsa84632
Down-regulation Phosphorylation FUNDC1 hsa139341
Up-regulation Expression MAP1LC3B hsa81631
Down-regulation Phosphorylation SRC hsa6714
Result Artesunate may be a promising strategy to mitigate sorafenib resistance in HCC via exacerbating AFAP1L2-SRC-FUNDC1 axis-dependent mitophagy.
Combination Pair ID: 95
Ref_55
Pair Name Amentoflavone, Sorafenib
Partner Name Amentoflavone
Disease Info [ICD-11: 2B51] Osteosarcoma Investigative
Biological Phenomena Induction-->Apoptosis
Gene Regulation Down-regulation Expression CFLAR hsa8837
Down-regulation Phosphorylation MAPK1 hsa5594
Down-regulation Expression MMP9 hsa4318
Down-regulation Phosphorylation NFKB1 hsa4790
Down-regulation Expression VEGFA hsa7422
Down-regulation Expression XIAP hsa331
In Vitro Model U2OS Osteosarcoma Homo sapiens (Human) CVCL_0042
Result Amentoflavone may sensitize OS to sorafenib treatment by inducing intrinsic and extrinsic apoptosis and inhibiting ERK/NF-κB signaling transduction.
Combination Pair ID: 649
Ref_56
Pair Name Amentoflavone, Sorafenib
Partner Name Amentoflavone
Disease Info [ICD-11: 2C12] Hepatocellular carcinoma Investigative
Biological Phenomena Induction-->Apoptosis
Gene Regulation Down-regulation Expression CASP3 hsa836
Down-regulation Expression CASP8 hsa841
Down-regulation Expression CASP9 hsa842
Down-regulation Expression CFLAR hsa8837
Down-regulation Phosphorylation MAPK3 hsa5595
Down-regulation Expression MCL1 hsa4170
Down-regulation Expression XIAP hsa331
In Vitro Model SK-HEP-1 Liver and intrahepatic bile duct epithelial neoplasm Homo sapiens (Human) CVCL_0525
In Vivo Model To establish the animal model, 1×10⁷ SK-Hep1 cells were suspended in 150 ul mix-ture of serum-free DMEM and matrigel (2: 1) and inoculated subcutaneously in the right legs of nude mice.
Result Our results demonstrated that amentoflavone significantly enhanced sorafenib-inhibited tumor growth and expression of ERK/AKT phosphorylation and anti-apoptotic proteins compared to single-agent treatment. Additionally, amentoflavone also triggered sorafenib-induced apoptosis through extrinsic and intrinsic apoptotic pathways.
Combination Pair ID: 439
Ref_57
Pair Name alpha-Mangostin, Sorafenib
Partner Name alpha-Mangostin
Disease Info [ICD-11: 2C12] Hepatocellular carcinoma Investigative
Biological Phenomena Induction-->Apoptosis
Gene Regulation Down-regulation Expression LRRC8A hsa56262
Down-regulation Phosphorylation MAPK1 hsa5594
Down-regulation Phosphorylation MTOR hsa2475
Up-regulation Expression PRKAA1 hsa5562
Up-regulation Expression RNF181 hsa51255
In Vivo Model Hep3B and MHCC97L cells (5×10⁶) were injected subcutaneously into the right flank of the male BALB/c nude mice (4–6 weeks old).
Result Our results highlight the synergistic effect of the combination of sorafenib and α-Mangostin, which indicates a potential treatment for advanced HCC for patients that are not sensitive to sorafenib therapy.
Combination Pair ID: 442
Ref_58
Pair Name alpha-Mangostin, Sorafenib
Partner Name alpha-Mangostin
Disease Info [ICD-11: 2C30] Melanoma Investigative
Biological Phenomena Induction-->Endoplasmic reticulum stress
Gene Regulation Down-regulation Phosphorylation AKT1 hsa207
Down-regulation Expression ATG5 hsa9474
Up-regulation Phosphorylation EIF2S1 hsa1965
Down-regulation Expression MAP1LC3A hsa84557
Up-regulation Expression MAP1LC3B hsa81631
Down-regulation Phosphorylation MAPK1 hsa5594
Down-regulation Expression MCL1 hsa4170
Down-regulation Expression MITF hsa4286
In Vitro Model SK-MEL-2 Melanoma Homo sapiens (Human) CVCL_0069
SK-MEL-30 Cutaneous melanoma Homo sapiens (Human) CVCL_0039
Result These data demonstrate an unanticipated synergy between α-Mangostin and sorafenib, with mechanistic actions that convert a known safe natural product to a candidate combinatorial therapeutic agent.
Combination Pair ID: 425
Ref_59
Pair Name Acteoside, Sorafenib
Partner Name Acteoside
Disease Info [ICD-11: 2C12] Hepatocellular carcinoma Investigative
Biological Phenomena Inhibition-->Angiogenesis
Gene Regulation Down-regulation Expression KLK1 hsa3816
Down-regulation Expression KLK10 hsa5655
Down-regulation Expression KLK2 hsa3817
Down-regulation Expression KLK4 hsa9622
Down-regulation Expression KLK9 hsa284366
Up-regulation Expression TP53 hsa7157
In Vitro Model BEL-7404 Human papillomavirus-related cervical adenocarcinoma Homo sapiens (Human) CVCL_6568
HLF Adult hepatocellular carcinoma Homo sapiens (Human) CVCL_2947
JHH-7 Adult hepatocellular carcinoma Homo sapiens (Human) CVCL_2805
In Vivo Model The BEL7404 cell suspensions were prepared (3×10⁶ cells) and injected subcutaneously into the right flank of athymic nude mice.
Result Acteoside exerts an antitumor effect possibly through its up-regulation of p53 levels as well as inhibition of KLK expression and angiogenesis. Acteoside could be useful as an adjunct in the treatment of advanced HCC in the clinic.
Reversing Drug Resistance
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Combination Pair ID: 34
Ref_60
Pair Name Vinpocetine, Sorafenib
Partner Name Vinpocetine
Disease Info [ICD-11: 2C12] Hepatocellular carcinoma Investigative
Biological Phenomena Induction-->Apoptosis
Gene Regulation Down-regulation Phosphorylation AKT1 hsa207
Up-regulation Cleavage CASP3 hsa836
Up-regulation Activity GSK3B hsa2932
Up-regulation Expression MAP1LC3A hsa84557
Down-regulation Expression MCL1 hsa4170
Down-regulation Phosphorylation MTOR hsa2475
Up-regulation Cleavage PARP1 hsa142
Down-regulation Expression PIK3CA hsa5290
In Vitro Model Hep-G2 Hepatoblastoma Homo sapiens (Human) CVCL_0027
Hep 3B2.1-7 Childhood hepatocellular carcinoma Homo sapiens (Human) CVCL_0326
Result Vinpocetine may be a potential candidate for sorafenib sensitization and HCC treatment, and our results may help to elucidate more effective therapeutic options for HCC patients with sorafenib resistance.
Combination Pair ID: 650
Ref_61
Pair Name Amentoflavone, Sorafenib
Partner Name Amentoflavone
Disease Info [ICD-11: 2C12] Hepatocellular carcinoma Investigative
Biological Phenomena Induction-->Apoptosis
Gene Regulation Up-regulation Cleavage CASP3 hsa836
Up-regulation Cleavage CASP8 hsa841
Down-regulation Expression CFLAR hsa8837
Down-regulation Expression MCL1 hsa4170
Down-regulation Expression XIAP hsa331
In Vitro Model SK-HEP-1 Liver and intrahepatic bile duct epithelial neoplasm Homo sapiens (Human) CVCL_0525
Result Amentoflavone not only reversed sorafenib-induced anti-apoptotic protein levels but also enhanced sorafenib-induced pro-apoptotic protein expression in SK-Hep1R cells. In conclusion, amentoflavone may be used as a sorafenib sensitizer to enhance sorafenib-induced cytotoxicity and trigger sorafenib-induced apoptosis through extrinsic and intrinsic pathways in SK-Hep1R cells.
Decreasing Drug Toxicity
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Combination Pair ID: 143
Ref_1
Pair Name Trifolirhizin, Sorafenib
Partner Name Trifolirhizin
Disease Info [ICD-11: 2C12] Hepatocellular carcinoma Investigative
Biological Phenomena Induction-->Blockade of cell cycle in G0/G1 phase
Gene Regulation Down-regulation Expression AKT1 hsa207
Up-regulation Activity CASP3 hsa836
Up-regulation Activity CASP9 hsa842
Down-regulation Expression MAPK1 hsa5594
In Vitro Model MHCC97-H Adult hepatocellular carcinoma Homo sapiens (Human) CVCL_4972
In Vivo Model Each mouse was subcuta-neously inoculated in the right flank with 100μl PBS (PH 7.4) contain-ing 1.5×10⁶ HepG2 cells.
Result Synergistic anticancer effect of flavonoids from Sophora alopecuroides with Sorafenib against hepatocellular carcinoma
Combination Pair ID: 223
Ref_2
Pair Name Lupeol, Sorafenib
Partner Name Lupeol
Disease Info [ICD-11: 2C12] Hepatocellular carcinoma Investigative
Biological Phenomena Induction-->DNA damage
Gene Regulation Up-regulation Expression FAM20C hsa56975
Up-regulation Expression ROS1 hsa6098
Down-regulation Expression TP53 hsa7157
In Vitro Model Huh-7 Adult hepatocellular carcinoma Homo sapiens (Human) CVCL_0336
Result Implication of Lupeol in compensating Sorafenib-induced perturbations of redox homeostasis: A preclinical study in mouse model
Combination Pair ID: 261
Ref_3
Pair Name Ilexgenin A, Sorafenib
Partner Name Ilexgenin A
Disease Info [ICD-11: 2C12] Hepatocellular carcinoma Investigative
Biological Phenomena Inhibition-->Angiogenesis
Gene Regulation Up-regulation Expression CASP3 hsa836
Up-regulation Expression CASP7 hsa840
Down-regulation Expression IL6 hsa3569
Down-regulation Expression MVD hsa4597
Down-regulation Expression PIK3CA hsa5290
Down-regulation Expression STAT3 hsa6774
Down-regulation Expression TNF hsa7124
Down-regulation Expression VEGFA hsa7422
In Vitro Model Hep-G2 Hepatoblastoma Homo sapiens (Human) CVCL_0027
Result The results described in the present study identifies Ilexgenin A as a promising therapeutic candidate that modulates inflammation, angiogenesis, and HCC growth.
Combination Pair ID: 993
Ref_4
Pair Name Hesperetin, Sorafenib
Partner Name Hesperetin
Disease Info [ICD-11: 2C12] Hepatocellular carcinoma Investigative
Biological Phenomena Induction-->Apoptosis
Gene Regulation Down-regulation Expression DNM1L hsa10059
In Vivo Model Swiss albino mice were orally administered sorafenib (100 mg/kg) alone or in combination with hesperetin (50 mg/kg) over 21 days.
Result Hesperetin exhibits potential as an adjunct to sorafenib, mitigating its side effects by attenuating its toxicity, enhancing efficacy, and potentially reducing the occurrence of sorafenib-induced resistance through the downregulation of hepatocyte growth factor levels.
Combination Pair ID: 330
Ref_5
Pair Name Eugenol, Sorafenib
Partner Name Eugenol
Disease Info [ICD-11: 2D10.Z] Thyroid cancer Investigative
Biological Phenomena Induction-->Apoptosis
Gene Regulation Up-regulation Cleavage CASP8 hsa841
Down-regulation Cleavage CASP9 hsa842
In Vitro Model 8305C Thyroid gland anaplastic carcinoma Homo sapiens (Human) CVCL_1053
Result The most potent apoptotic effect was achieved with sorafenib and eugenol at their IC50. Lower doses of sorafenib could be used with eugenol to improve its efficacy while reducing its side effects.
Combination Pair ID: 600
Ref_6
Pair Name Escin, Sorafenib
Partner Name Escin
Disease Info [ICD-11: 2C25] Lung cancer Investigative
Biological Phenomena Induction-->Blockade of cell cycle in G0/G1 phase
Gene Regulation Down-regulation Expression ATG5 hsa9474
Up-regulation Expression MAP1LC3B hsa81631
Up-regulation Expression SQSTM1 hsa8878
In Vitro Model A-549 Lung adenocarcinoma Homo sapiens (Human) CVCL_0023
NCI-H460 Lung large cell carcinoma Homo sapiens (Human) CVCL_0459
In Vivo Model Wistar rats, aged between 6 and 8 weeks, weighing 150–200 g (male),were uesd in study.
Result This combination also selectively targeted G0/G1 phase of cancer cells. In in vivo study, the combination reduced tumour load and lower elevated serum biochemical parameters. The combination of sorafenib/escin synergistically inhibits autophagy to induce late apoptosis in lung cancer cells' G0/G1 phase.
Combination Pair ID: 429
Ref_7
Pair Name Carvacrol, Sorafenib
Partner Name Carvacrol
Disease Info [ICD-11: 2C12] Hepatocellular carcinoma Investigative
Biological Phenomena Inhibition-->Epithelial-mesenchymal transition
Gene Regulation Down-regulation Expression ABCG2 hsa9429
Up-regulation Expression BAX hsa581
Down-regulation Expression BCL2 hsa596
Down-regulation Expression CCND1 hsa595
Up-regulation Expression GSS hsa2937
Down-regulation Expression HIF1A hsa3091
Up-regulation Expression IL6 hsa3569
Down-regulation Expression LDHA hsa3939
Down-regulation Expression NOTCH1 hsa4851
Down-regulation Expression SALL4 hsa57167
Down-regulation Expression TGFB1 hsa7040
Up-regulation Expression TNF hsa7124
Down-regulation Expression TRPM7 hsa54822
Down-regulation Expression VEGFA hsa7422
Down-regulation Expression VIM hsa7431
In Vivo Model A preliminary study was conducted using 200 mg/kg of TAA dissolved in 0.2 mL of normal saline and given intraperitoneal (i.p.) twice a week for 16 weeks to induce HCC.
Result CARV/Sora is a promising combination for tumor suppression and overcoming Sora resistance and cardiotoxicity in HCC by modulating TRPM7. To our best knowledge, this study represents the first study to investigate the efficiency of CARV/ Sora on the HCC rat model. Moreover, no previous studies have reported the effect of inhibiting TRPM7 on HCC.
Combination Pair ID: 36
Ref_8
Pair Name Amygdalin, Sorafenib
Partner Name Amygdalin
Disease Info [ICD-11: 2D91] Ehrlich ascites carcinoma Investigative
Gene Regulation Down-regulation Expression MMP9 hsa4318
Up-regulation Expression NFE2L2 hsa4780
Up-regulation Expression SOD1 hsa6647
Down-regulation Expression VEGFA hsa7422
In Vitro Model EAC-E2G8 Malignant neoplasms of the mouse mammary gland Mus musculus (Mouse) CVCL_WJ08
In Vivo Model Each mouse was injected with 200 mL of 1×10⁶ EAC cells.
Result Amy improved the antitumor effect of Sor and had a protective role on liver damage induced by EAC in mice.
Combination Pair ID: 144
Ref_9
Pair Name (-)-Catechin gallate, Sorafenib
Partner Name (-)-Catechin gallate
Disease Info [ICD-11: 2C12] Hepatocellular carcinoma Investigative
Biological Phenomena Inhibition-->Angiogenesis
Gene Regulation Down-regulation Expression VEGFA hsa7422
In Vivo Model Rats were randomized and allocated into four groups, consisting of 7 rats, except the control (K) group, which contained four rats, with a minimal sample size of three. Subsequently, DEN was injected intraperitoneally in the abdominal area below the umbilicus on 21 rats for two treatment groups and a control group, with 70 mg/kg BW/week for ten weeks.
Result Standard-dose Sorafenib and the combination of low-dose Sorafenib and epigallo-3-catechin gallate have similar effectivity in reducing the expression of microvascular density and could prevent resistance and lower toxicity effects.
04. Reference
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