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Drug Details
01. General Information
Name Gemcitabine
PubChem CID 60750
Molecular Weight 263.20g/mol
Synonyms

gemcitabine, 95058-81-4, 2'-Deoxy-2',2'-difluorocytidine, 2',2'-Difluorodeoxycytidine, dFdC, Cytidine, 2'-deoxy-2',2'-difluoro-, Gemcitabine free base, 2',2'-difluoro-2'-deoxycytidine, 103882-84-4, 4-amino-1-[(2R,4R,5R)-3,3-difluoro-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-1,2-dihydropyrimidin-2-one, LY188011, 4-amino-1-((2R,4R,5R)-3,3-difluoro-4-hydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)pyrimidin-2(1H)-one, 95058-81-4 (free base), B76N6SBZ8R, LY 188011, 4-Amino-1-[(2R,4R,5R)-3,3-difluoro-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidin-2-one, Gamcitabine, Gemcitabina, CHEBI:175901, DFdCyd, NSC-613327, Gemcitabinum, Folfugem, Gemcel, Zefei, GemLip, 4-amino-1-((2R,4R,5R)-3,3-difluoro-4-hydroxy-5-(hydroxymethyl)-tetrahydrofuran-2-yl)pyrimidin-2(1H)-one, Gemcitabinum [INN-Latin], Gemcitabina [INN-Spanish], C9H11F2N3O4, Gemzar (hydrochloride), SR-05000001491, Gemcitabine (USAN/INN), UNII-B76N6SBZ8R, 2',2'-DiF-dC, Gemcitabine [USAN:INN:BAN], CCRIS 8984, MFCD00869720, HSDB 7567, 2vpp, gemcitabine (Gemzar), NSC 613327, 4pd5, GEMCITABINE [MI], GEMCITABINE [INN], 2'-Deoxy-.beta.-D-2',2'-difluorocytidine, GEMCITABINE [HSDB], GEMCITABINE [USAN], CHEMBL888, GEMCITABINE [VANDF], SCHEMBL4295, GEMCITABINE [WHO-DD], GTPL4793, DTXSID3040487, 2'deoxy-2',2'-difluorocytidine, BCPP000219, BDBM429521, GLXC-04598, HMS2089P10, HMS3715N07, 2`-Deoxy-2`,2`-difluorocytidine, med.21724, Compound Gemcitabine, DL-215, s1714, AKOS015920303, Cytidine, 2'-deoxy-2',2'-difluoro-2'-Deoxy-.beta.-D-2',2'-difluorocytidine, BCP9000721, CCG-221183, CS-0643, DB00441, GS-3582, 4-Amino-1-[3,3-difluoro-4-hydroxy-5-(hydroxymethyl) tetrahydrofuran-2-yl]-1H-pyrimidin-2-one, NCGC00168784-02, NCGC00168784-08, NCGC00168784-12, BP-58640, HY-17026, G0544, NS00000342, SW199649-2, C07650, D02368, EN300-267822, AB01274777-01, AB01274777-02, AB01274777_05, AB01274777_06, Q414143, J-001056, SR-05000001491-1, SR-05000001491-2, BRD-K15108141-001-04-1, Z1741982024, 4-AMINO-1-[(2R,4R,5R)-3,3-DIFLUORO-4-HYDROXY-5-(HYDROXYMETHYL)TETRAHYDRO-2-FURANYL]-2(1H)-PYRIMIDINONE, 4-amino-1-[(2R,4R,5R)-3,3-difluoro-4-hydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl]pyrimidin-2-one
Drug Type Small molecule
Formula C₉H₁₁F₂N₃O₄
SMILES C1=CN(C(=O)N=C1N)C2C(C(C(O2)CO)O)(F)F
InChI 1S/C9H11F2N3O4/c10-9(11)6(16)4(3-15)18-7(9)14-2-1-5(12)13-8(14)17/h1-2,4,6-7,15-16H,3H2,(H2,12,13,17)/t4-,6-,7-/m1/s1
InChIKey SDUQYLNIPVEERB-QPPQHZFASA-N
CAS Number 95058-81-4
ChEMBL ID CHEMBL888
ChEBI ID CHEBI:175901
TTD ID D03UVS
Drug Bank ID DB00441
KEGG ID C07650
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
02. Combinatorial Therapeutic Effect(s)
Synergistic Effect
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Enhancing Drug Efficacy
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Combination Pair ID: 757
Ref_1
Pair Name Thymoquinone, Gemcitabine
Partner Name Thymoquinone
Disease Info [ICD-11: 2C10] Pancreatic cancer Investigative
Biological Phenomena Induction-->Apoptosis
Gene Regulation Down-regulation Expression COL1A1 hsa1277
Down-regulation Expression COL3A1 hsa1281
Down-regulation Expression COL5A1 hsa1289
Down-regulation Expression HIF1A hsa3091
Down-regulation Expression SMAD2 hsa4087
Down-regulation Expression SMAD3 hsa4088
Down-regulation Expression TGFB1 hsa7040
In Vitro Model PANC-1 Pancreatic ductal adenocarcinoma Homo sapiens (Human) CVCL_0480
In Vivo Model PANC-1 cells cultured under normoxic conditions formed subcutaneous tumors in nude mice, with a tumorigenic cycle of 4 weeks (grouping: a total of 9 mice were divided into three groups with 3 mice per group; age: 6– weeks; weight: 200–220 g).
Result TQ can promote apoptosis, inhibit migration, invasion, and metastasis, and enhance the sensitivity to GEM. The underlying mechanism may involve the regulation of ECM production through the TGFβ/Smad pathway, in which HIF-1α plays a key role.
Combination Pair ID: 902
Ref_2
Pair Name Sulforaphane, Gemcitabine
Partner Name Sulforaphane
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
Down-regulation Phosphorylation CDC25C hsa995
Up-regulation Expression CDKN1A hsa1026
Up-regulation Phosphorylation CHEK2 hsa11200
In Vitro Model HuCC-T1 Intrahepatic cholangiocarcinoma Homo sapiens (Human) CVCL_0324
HuH-28 Intrahepatic cholangiocarcinoma Homo sapiens (Human) CVCL_2955
In Vivo Model A million cells were suspended in 200 μL of medium containing Matrigel (Corning, Tewksbury, MA, USA; 1:1), and the same type of 1×10⁶ cells was inoculated subcutaneously into the bilateral flanks of each mouse.
Result Sulforaphane Potentiates Gemcitabine-Mediated Anti-Cancer Effects against Intrahepatic Cholangiocarcinoma by Inhibiting HDAC Activity
Combination Pair ID: 870
Ref_3
Pair Name Shogaol, Gemcitabine
Partner Name Shogaol
Disease Info [ICD-11: 2C10.0] Pancreatic ductal adenocarcinoma Investigative
Gene Regulation Down-regulation Expression BIRC5 hsa332
Up-regulation Cleavage CASP3 hsa836
Down-regulation Expression CCND1 hsa595
Down-regulation Expression COX2 hsa4513
Down-regulation Activity NFKB1 hsa4790
Up-regulation Cleavage PARP1 hsa142
Down-regulation Phosphorylation RELA hsa5970
Down-regulation Activity TLR4 hsa7099
Down-regulation Expression XIAP hsa331
In Vitro Model PANC-1 Pancreatic ductal adenocarcinoma Homo sapiens (Human) CVCL_0480
BxPC-3 Pancreatic ductal adenocarcinoma Homo sapiens (Human) CVCL_0186
In Vivo Model Male BALB/c immunodeficient nude mice were injected with PANC-1 cells (1×10⁷) with matrigel (100 uL) to the right flank of each mice.
Result Our results suggest that 6-shogaol can inhibit the growth of human pancreatic tumors and sensitize them to gemcitabine by suppressing of TLR4/NF-κB-mediated inflammatory pathways linked to tumorigenesis.
Combination Pair ID: 725
Ref_4
Pair Name Shikonin, Gemcitabine
Partner Name Shikonin
Disease Info [ICD-11: 2C10] Pancreatic cancer Investigative
Biological Phenomena Induction-->Apoptosis
Gene Regulation Down-regulation Expression BCL2 hsa596
Down-regulation Expression BCL-xL hsa598
Up-regulation Activity CASP3 hsa836
Up-regulation Activity CASP9 hsa842
Down-regulation Expression CCND1 hsa595
Down-regulation Activity CDH13 hsa1012
Down-regulation Expression COX2 hsa4513
Down-regulation Expression MMP9 hsa4318
Down-regulation Expression MYC hsa4609
Down-regulation Expression VEGFA hsa7422
Down-regulation Expression XIAP hsa331
In Vitro Model PANC-1 Pancreatic ductal adenocarcinoma Homo sapiens (Human) CVCL_0480
BxPC-3 Pancreatic ductal adenocarcinoma Homo sapiens (Human) CVCL_0186
AsPC-1 Pancreatic ductal adenocarcinoma Homo sapiens (Human) CVCL_0152
In Vivo Model Tumors were established by subcutaneous injection of 5×10⁶ BxPC-3 cells into the flanks of male nude BALB/c mice.
Result Our results suggest that shikonin can suppress the growth of human pancreatic tumors and potentiate the antitumor effects of gemcitabine through the suppression of NF-κB and NF-κB-regulated gene products.
Combination Pair ID: 525
Ref_5
Pair Name Se-Methylselenocysteine, Gemcitabine
Partner Name Se-Methylselenocysteine
Disease Info [ICD-11: 2C25] Lung cancer Investigative
Biological Phenomena Induction-->Apoptosis
Gene Regulation Up-regulation Expression CASP3 hsa836
Up-regulation Cleavage PARP1 hsa142
In Vitro Model A-549 Lung adenocarcinoma Homo sapiens (Human) CVCL_0023
Result Antitumor study in Ehrlich solid tumor model showed the efficacy of MSC combination with GEM for the enhanced antitumor activity. The proposed combination demonstrated the potential for further translational studies.
Combination Pair ID: 266
Ref_6
Pair Name Sclareolide, Gemcitabine
Partner Name Sclareolide
Disease Info [ICD-11: 2C10] Pancreatic cancer Investigative
Biological Phenomena Induction-->Apoptosis
Gene Regulation Up-regulation Expression CASP3 hsa836
Up-regulation Expression CDH1 hsa999
Down-regulation Expression GLI1 hsa2735
Up-regulation Expression PARP1 hsa142
Down-regulation Expression RRM1 hsa6240
Up-regulation Expression SLC29A1 hsa2030
Down-regulation Expression SNAI2 hsa6591
Down-regulation Expression TWIST1 hsa7291
In Vitro Model PANC-1 Pancreatic ductal adenocarcinoma Homo sapiens (Human) CVCL_0480
AsPC-1 Pancreatic ductal adenocarcinoma Homo sapiens (Human) CVCL_0152
In Vivo Model Each BALB/c nude mouse was subcutaneously inoculated with 5×10⁶ Panc-1 or GR-Panc-1 cells in their right and left hind footpads.
Result Sclareolide enhances gemcitabine‑induced cell death through mediating the NICD and Gli1 pathways in gemcitabine‑resistant human pancreatic cancer
Combination Pair ID: 380
Ref_7
Pair Name Resveratrol, Gemcitabine
Partner Name Resveratrol
Disease Info [ICD-11: 2C10] Pancreatic cancer Investigative
Biological Phenomena Induction-->Apoptosis
Gene Regulation Up-regulation Phosphorylation GSK3B hsa2932
Down-regulation Expression VEGFA hsa7422
In Vitro Model Capan-2 Pancreatic ductal adenocarcinoma Homo sapiens (Human) CVCL_0026
MIA PaCa-2 Pancreatic ductal adenocarcinoma Homo sapiens (Human) CVCL_0428
PANC-1 Pancreatic ductal adenocarcinoma Homo sapiens (Human) CVCL_0480
In Vivo Model 5×10⁶ MiaPaCa2 cells were suspended in DMEM medium and transplanted subcutaneously in each nude mouse.
Result These results suggest that VEGF-B signaling pathway plays an important role in the development of PaCa and combination of GEM and RSV would be a promising modality for clinical PaCa therapy.
Combination Pair ID: 925
Ref_8
Pair Name Pristimerin, Gemcitabine
Partner Name Pristimerin
Disease Info [ICD-11: 2C10.0] Pancreatic ductal adenocarcinoma Investigative
Biological Phenomena Induction-->DNA damage
Gene Regulation Down-regulation Phosphorylation CHEK1 hsa1111
Down-regulation Expression TP53 hsa7157
In Vitro Model AsPC-1 Pancreatic ductal adenocarcinoma Homo sapiens (Human) CVCL_0152
BxPC-3 Pancreatic ductal adenocarcinoma Homo sapiens (Human) CVCL_0186
PANC-1 Pancreatic ductal adenocarcinoma Homo sapiens (Human) CVCL_0480
Result These results show that pristimerin acts as a naturally occurring inhibitor of RSR, and a novel therapeutic strategy of combining pristimerin and gemcitabine deserves further detailed investigation in PC models in vivo.
Combination Pair ID: 798
Ref_9
Pair Name Piceatannol, Gemcitabine
Partner Name Piceatannol
Disease Info [ICD-11: 2C25] Lung cancer Investigative
Biological Phenomena Induction-->Apoptosis
Gene Regulation Up-regulation Expression BAK1 hsa578
Up-regulation Expression BID hsa637
In Vitro Model A-549 Lung adenocarcinoma Homo sapiens (Human) CVCL_0023
Result The findings from this study show that piceatannol can enhance the cytotoxic effects of gemcitabine by enhancing expression of the proapoptotic protein Bak, thereby providing the rational basis for a novel combination strategy for the treatment of NSCLC.
Combination Pair ID: 959
Ref_10
Pair Name Periplocin, Gemcitabine
Partner Name Periplocin
Disease Info [ICD-11: 2C10] Pancreatic cancer Investigative
Biological Phenomena Induction-->Blockade of cell cycle in G0/G1 phase
Gene Regulation Down-regulation Expression BCL-xL hsa598
Down-regulation Expression BIRC5 hsa332
Up-regulation Cleavage CASP8 hsa841
Down-regulation Expression CCND1 hsa595
Down-regulation Expression CDK2 hsa1017
Down-regulation Expression CDK4 hsa1019
Down-regulation Expression CDK6 hsa1021
Down-regulation Expression FOS hsa2353
Down-regulation Expression HMOX1 hsa3162
Up-regulation Expression KEAP1 hsa9817
Down-regulation Expression NFE2L2 hsa4780
Up-regulation Cleavage PARP1 hsa142
Down-regulation Expression PRDX1 hsa5052
Down-regulation Phosphorylation RELA hsa5970
In Vitro Model PANC-1 Pancreatic ductal adenocarcinoma Homo sapiens (Human) CVCL_0480
HEK293 Healthy Homo sapiens (Human) CVCL_0045
In Vivo Model PANC-1 and PANC-GR cell suspension (4×10⁶ cells per mouse mix with Matrigel 1:1) was subcutaneously injected into the right flank of mice and tumors were maintained until tumor volume reached 80 mm3.
Result Periplocin exerts antitumor activity by regulating Nrf2-mediated signaling pathway in gemcitabine-resistant pancreatic cancer cells
Combination Pair ID: 193
Ref_11
Pair Name Oleanolic Acid, Gemcitabine
Partner Name Oleanolic Acid
Disease Info [ICD-11: 2C10] Pancreatic cancer Investigative
Biological Phenomena Induction-->Mitochondrial damage
Gene Regulation Down-regulation Expression EGFR hsa1956
Down-regulation Expression EZH2 hsa2146
Down-regulation Expression MAP2K7 hsa5609
Down-regulation Expression MAPK1 hsa5594
Down-regulation Expression SPINK1 hsa6690
In Vitro Model AsPC-1 Pancreatic ductal adenocarcinoma Homo sapiens (Human) CVCL_0152
MIA PaCa-2 Pancreatic ductal adenocarcinoma Homo sapiens (Human) CVCL_0428
Result We found an interesting finding that the 73-03 in combination with GCB can improve GCB efficacy and decrease PCa resistance, which induced apoptosis and mitochondrial damage through epigenetic inhibition of SPINK1 transcription by miR-421 up-regulation. This was the first study that used OA derivatives on GCB-resistant PCa cells, so this combined strategy warrants further investigation.
Combination Pair ID: 957
Ref_12
Pair Name Noscapine, Gemcitabine
Partner Name Noscapine
Disease Info [ICD-11: 2C25] Lung cancer Investigative
Biological Phenomena Inhibition-->Angiogenesis
Gene Regulation Up-regulation Expression BAX hsa581
Down-regulation Expression BCL2 hsa596
Up-regulation Expression BID hsa637
Down-regulation Expression BIRC5 hsa332
Up-regulation Cleavage CASP3 hsa836
Up-regulation Expression CASP3 hsa836
Up-regulation Expression CASP8 hsa841
Up-regulation Expression CASP9 hsa842
Down-regulation Expression CCND1 hsa595
Up-regulation Expression CDKN1A hsa1026
Up-regulation Cleavage PARP1 hsa142
Down-regulation Expression PARP1 hsa142
Up-regulation Expression TP53 hsa7157
Down-regulation Expression VEGFA hsa7422
In Vitro Model NCI-H460 Lung large cell carcinoma Homo sapiens (Human) CVCL_0459
A-549 Lung adenocarcinoma Homo sapiens (Human) CVCL_0023
In Vivo Model For a xenograft model, 3×10⁶ human H460 cells were injected subcutaneously into the right flanks of the mice.
Result Nos potentiated the anticancer activity of Gem in an additive to synergistic manner against lung cancer via antiangiogenic and apoptotic pathways. These findings suggest potential benefit for use of NGC chemotherapy for treatment of lung cancer.
Combination Pair ID: 520
Ref_13
Pair Name Niacinamide, Gemcitabine
Partner Name Niacinamide
Disease Info [ICD-11: 2C10] Pancreatic cancer Investigative
Biological Phenomena Induction-->Immunomodulatory
Gene Regulation Up-regulation Expression CCL21 hsa6366
Down-regulation Expression HABP2 hsa3026
Up-regulation Expression PECAM1 hsa5175
In Vitro Model Panc02 Mouse pancreatic ductal adenocarcinoma Mus musculus (Mouse) CVCL_D627
In Vivo Model The spleen/pancreas was gently retracted and positioned to allow injection of Panc-02 tumor cells (1×10⁶/50 µL phosphate-buffered saline (PBS)) directly into the pancreas, from the tail all the way to the head of the pancreas.
Result This study highlights the potential of NAM+GEM as immunotherapy for advanced pancreatic cancer.
Combination Pair ID: 222
Ref_14
Pair Name Maslinic acid, Gemcitabine
Partner Name Maslinic acid
Disease Info [ICD-11: 2C94] Bladder cancer Investigative
Biological Phenomena Induction-->Apoptosis
Gene Regulation Down-regulation Expression BAX hsa581
Down-regulation Expression BCL2 hsa596
Down-regulation Expression CCND1 hsa595
Down-regulation Expression MMP2 hsa4313
Down-regulation Expression MMP9 hsa4318
Down-regulation Activity NFKB1 hsa4790
In Vitro Model EH-GB1 Gallbladder carcinoma Homo sapiens (Human) CVCL_IU73
EH-GB2 Gallbladder carcinoma Homo sapiens (Human) CVCL_6899
GBC-SD Gallbladder carcinoma Homo sapiens (Human) CVCL_6903
In Vivo Model EH-GB2 tumor cells were subcutaneously injected into the mice (2×10⁶ cells/mouse).
Result The results suggest that MA potentiates the antitumor effects of GEM in human GBC cell lines by suppressing the activation of NF-κB and its dowstream gene products, which are involved in survival signaling.
Combination Pair ID: 849
Ref_15
Pair Name Luteolin, Gemcitabine
Partner Name Luteolin
Disease Info [ICD-11: 2C10.0] Pancreatic ductal adenocarcinoma Investigative
Biological Phenomena Induction-->Apoptosis
Gene Regulation Up-regulation Expression BAX hsa581
Down-regulation Expression BCL2 hsa596
Up-regulation Expression CASP3 hsa836
Down-regulation Expression CDH13 hsa1012
Down-regulation Expression GSK3B hsa2932
Down-regulation Expression KRAS hsa3845
In Vitro Model BxPC-3 Pancreatic ductal adenocarcinoma Homo sapiens (Human) CVCL_0186
In Vivo Model Male athymic nude mice were inoculated with BxPC-3 cells (1×10⁶ cells/mouse) cells
Result Luteolin + Gem promoted apoptotic cell death in pancreatic tumor cells in vivo through inhibition of the K-ras/GSK-3β/NF-κB signaling pathway, leading to a reduction in the Bcl-2/Bax ratio, release of cytochrome c, and activation of caspase 3.
Combination Pair ID: 417
Ref_16
Pair Name Icariin, Gemcitabine
Partner Name Icariin
Disease Info [ICD-11: 2C94] Bladder cancer Investigative
Biological Phenomena Induction-->Blockade of cell cycle in G0/G1 phase
Gene Regulation Down-regulation Expression BCL2 hsa596
Down-regulation Expression BCL-xL hsa598
Down-regulation Expression BIRC5 hsa332
Down-regulation Expression CASP3 hsa836
Down-regulation Activity NFKB1 hsa4790
Up-regulation Expression PARP1 hsa142
In Vitro Model GBC-SD Gallbladder carcinoma Homo sapiens (Human) CVCL_6903
SGC-996 Gallbladder carcinoma Homo sapiens (Human) CVCL_M737
In Vivo Model 1×10⁵ GBC-SD cells were injected subcutaneously into the right and left abdominal regions with a gauge needle.
Result Icariin, by suppressing NF-κB activity, exerts antitumor activity, and potentiates the antitumor activity of gemcitabine in gallbladder cancer. Combined administration of gemcitabine and icariin may offer a better therapeutic option for the patients with gallbladder cancer.
Combination Pair ID: 431
Ref_17
Pair Name Hypericin, Gemcitabine
Partner Name Hypericin
Disease Info [ICD-11: 2C10] Pancreatic cancer Investigative
Biological Phenomena Induction-->Apoptosis
Gene Regulation Up-regulation Expression BAX hsa581
Down-regulation Expression BCL2 hsa596
Up-regulation Cleavage CASP3 hsa836
Up-regulation Cleavage CASP9 hsa842
Up-regulation Expression CYCS hsa54205
Down-regulation Expression DCTPP1 hsa79077
Down-regulation Expression H6PD hsa9563
Up-regulation Cleavage PARP1 hsa142
In Vitro Model Capan-2 Pancreatic ductal adenocarcinoma Homo sapiens (Human) CVCL_0026
Result We demonstrated that Gem combined HY-PDT could inhibit the proliferation of Capan-2 cells and induce cell apoptosis. HY-PDT combined with Gem had a great potential on pancreatic cancer treatment clinically.
Combination Pair ID: 496
Ref_18
Pair Name Hispidin, Gemcitabine
Partner Name Hispidin
Disease Info [ICD-11: 2C10] Pancreatic cancer Investigative
Gene Regulation Down-regulation Expression BCL2 hsa596
Up-regulation Cleavage CASP3 hsa836
Down-regulation Expression CD44 hsa960
Down-regulation Expression NANOG hsa79923
Down-regulation Expression NFKB1 hsa4790
Up-regulation Cleavage PARP1 hsa142
Down-regulation Expression SOX2 hsa6657
Down-regulation Expression TP53 hsa7157
In Vitro Model BxPC-3 Pancreatic ductal adenocarcinoma Homo sapiens (Human) CVCL_0186
AsPC-1 Pancreatic ductal adenocarcinoma Homo sapiens (Human) CVCL_0152
Result Hispidin might be a novel chemosensitizer for gemcitabine and a potential synergistic agent for increasing the therapeutic index of gemcitabine as a treatment for pancreatic cancer.
Combination Pair ID: 946
Ref_19
Pair Name Guggulsterone, Gemcitabine
Partner Name Guggulsterone
Disease Info [ICD-11: 2C10.0] Pancreatic ductal adenocarcinoma Investigative
Biological Phenomena Induction-->Apoptosis
Gene Regulation Down-regulation Phosphorylation AKT1 hsa207
Up-regulation Expression BAX hsa581
Down-regulation Expression BCL2 hsa596
Up-regulation Phosphorylation MAPK8 hsa5599
Down-regulation Activity NFKB1 hsa4790
In Vitro Model MIA PaCa-2 Pancreatic ductal adenocarcinoma Homo sapiens (Human) CVCL_0428
PANC-1 Pancreatic ductal adenocarcinoma Homo sapiens (Human) CVCL_0480
In Vivo Model To ceate the subcutaneous xenograft model, mice were subcutaneously inoculated with MiaPaCa-2 cells (1×10⁶cells/mouse) in 1 mL of Matrigel.
Result The combination of guggulsterone to gemcitabine enhanced antitumor efficacy through apoptosis induction by suppressing Akt and nuclear factor KappaB activity and by modulating apoptosis-related protein expression in pancreatic cancer
Combination Pair ID: 202
Ref_20
Pair Name Ginsenoside Rh2, Gemcitabine
Partner Name Ginsenoside Rh2
Disease Info [ICD-11: 2C10] Pancreatic cancer Investigative
Biological Phenomena Induction-->Immunomodulatory
Gene Regulation Up-regulation Expression BAX hsa581
Up-regulation Expression BCL10 hsa8915
Down-regulation Expression BCL2 hsa596
Up-regulation Expression CARD9 hsa64170
Up-regulation Cleavage CASP3 hsa836
Up-regulation Expression MALT1 hsa10892
Up-regulation Expression NFKB1 hsa4790
In Vitro Model Panc02 Mouse pancreatic ductal adenocarcinoma Mus musculus (Mouse) CVCL_D627
PANC-1 Pancreatic ductal adenocarcinoma Homo sapiens (Human) CVCL_0480
In Vivo Model Orthotopic mouse model: Panc02 cells engineered to stably express firefly luciferase (1×10⁶) were mixed in an equal volume of Matrigel and were injected into the tail of pancreas of each mouse.
Result Rh2 activation of DCs may remodel the cold TIME and optimize GEM chemotherapy for future therapeutic use.
Combination Pair ID: 941
Ref_21
Pair Name Geraniol, Gemcitabine
Partner Name Geraniol
Disease Info [ICD-11: 2C10.0] Pancreatic ductal adenocarcinoma Investigative
Biological Phenomena Induction-->Apoptosis
In Vitro Model BxPC-3 Pancreatic ductal adenocarcinoma Homo sapiens (Human) CVCL_0186
Result Geraniol inhibited the proliferation of BXPC-3 cells. Geraniol significantly increased the antiproliferative and apoptosis-inducing effects of gemcitabine on BXPC-3 cells. Maximum inhibition of BXPC-3 cells was achieved with geraniol treatment for 24 h before gemcitabine treatment.
Combination Pair ID: 928
Ref_22
Pair Name Gamma-Tocotrienol, Gemcitabine
Partner Name Gamma-Tocotrienol
Disease Info [ICD-11: 2C10] Pancreatic cancer Investigative
Biological Phenomena Induction-->Apoptosis
Gene Regulation Down-regulation Expression BCL2 hsa596
Down-regulation Expression BCL-xL hsa598
Down-regulation Expression BIRC2 hsa329
Up-regulation Activity CASP3 hsa836
Up-regulation Activity CASP9 hsa842
Down-regulation Expression CCND1 hsa595
Down-regulation Expression COX2 hsa4513
Down-regulation Expression CXCR4 hsa7852
Down-regulation Expression MMP9 hsa4318
Down-regulation Expression MYC hsa4609
Down-regulation Expression NFKB1 hsa4790
Down-regulation Expression VEGFA hsa7422
In Vitro Model MIA PaCa-2 Pancreatic ductal adenocarcinoma Homo sapiens (Human) CVCL_0428
In Vivo Model MIA PaCa-2 cells (1×10⁶) in 100 µL PBS were injected into the subcapsular region of the pancreas with a 27-gauge needle and a calibrated push button-controlled dispensing device.
Result Our findings suggest that γ-T3 can inhibit the growth of human pancreatic tumors and sensitize them to gemcitabine by suppressing NF-κB-mediated inflammatory pathways linked to tumorigenesis.
Combination Pair ID: 489
Ref_23
Pair Name Gambogic Acid, Gemcitabine
Partner Name Gambogic Acid
Disease Info [ICD-11: 2C25] Lung cancer Investigative
Biological Phenomena Induction-->Apoptosis
Gene Regulation Up-regulation Expression BAK1 hsa578
Down-regulation Expression BCL2 hsa596
Up-regulation Cleavage CASP3 hsa836
Up-regulation Cleavage PARP1 hsa142
Down-regulation Expression RRM2 hsa6241
In Vitro Model A-549 Lung adenocarcinoma Homo sapiens (Human) CVCL_0023
NCI-H1299 Lung large cell carcinoma Homo sapiens (Human) CVCL_0060
Result These results offer a rationale to evaluate the clinical translational possibility of GA as adjuvant therapy to overcome Gem resistance. This combination regimen can be a new therapeutic concept to eradicate this devastating disease.
Combination Pair ID: 490
Ref_24
Pair Name Gambogic Acid, Gemcitabine
Partner Name Gambogic Acid
Disease Info [ICD-11: 2C10] Pancreatic cancer Investigative
Biological Phenomena Induction-->Blockade of cell cycle in S phase
Gene Regulation Down-regulation Phosphorylation AKT1 hsa207
Up-regulation Expression BAX hsa581
Down-regulation Expression BCL2 hsa596
Up-regulation Expression CASP3 hsa836
Up-regulation Expression CASP9 hsa842
Down-regulation Expression E2F1 hsa1869
Down-regulation Phosphorylation MAPK1 hsa5594
Up-regulation Expression PARP1 hsa142
Down-regulation Expression RRM1 hsa6240
Down-regulation Expression RRM2 hsa6241
In Vitro Model BxPC-3 Pancreatic ductal adenocarcinoma Homo sapiens (Human) CVCL_0186
PANC-1 Pancreatic ductal adenocarcinoma Homo sapiens (Human) CVCL_0480
MIA PaCa-2 Pancreatic ductal adenocarcinoma Homo sapiens (Human) CVCL_0428
SW1990 Pancreatic adenocarcinoma Homo sapiens (Human) CVCL_1723
In Vivo Model The BxPC-3 cells (5×10⁶) were subcutaneously inoculated into the right thigh of each mouse.
Result These results demonstrate that gambogic acid sensitizes pancreatic cancer cells to gemcitabine in vitro and in vivo by inhibiting the activation of the ERK/E2F1/RRM2 signaling pathway. The results also indicate that gambogic acid treatment combined with gemcitabine might be a promising chemotherapy strategy for pancreatic cancer.
Combination Pair ID: 914
Ref_25
Pair Name Fucoxanthin, Gemcitabine
Partner Name Fucoxanthin
Disease Info [ICD-11: 2C10] Pancreatic cancer Investigative
Biological Phenomena Induction-->Apoptosis
In Vitro Model MIA PaCa-2 Pancreatic ductal adenocarcinoma Homo sapiens (Human) CVCL_0428
PANC-1 Pancreatic ductal adenocarcinoma Homo sapiens (Human) CVCL_0480
Result Fucoxanthin improved the cytotoxicity of gemcitabine on human pancreatic cancer cells at concentrations that were not cytotoxic to non-cancer cells. Thus, fucoxanthin has the potential to be used as an adjunct in pancreatic cancer treatment.
Combination Pair ID: 21
Ref_26
Pair Name Evodiamine, Gemcitabine
Partner Name Evodiamine
Disease Info [ICD-11: 2B62.Z] Tongue cancer Investigative
Biological Phenomena Induction-->Apoptosis
Gene Regulation Down-regulation Expression BCL2 hsa596
Down-regulation Expression BCL-xL hsa598
Down-regulation Expression RELA hsa5970
In Vitro Model CAL-27 Tongue adenosquamous carcinoma Homo sapiens (Human) CVCL_1107
Tca8113 Human papillomavirus-related cervical adenocarcinoma Homo sapiens (Human) CVCL_6851
In Vivo Model CAL-27 cells (2×10⁶) were injected subcutaneously into the right armpit regions of nude mice.
Result The results of this study showed that EVO may inhibit cancer cells by suppressing NF-κB activity, and in combination with GEM, it may increase the chemosensitivity of tongue squamous cancer cells, thereby improving the treatment response.
Combination Pair ID: 784
Ref_27
Pair Name Eugenol, Gemcitabine
Partner Name Eugenol
Disease Info [ICD-11: 2C77] Cervical cancer Investigative
Biological Phenomena Induction-->Apoptosis
Gene Regulation Down-regulation Expression BCL2 hsa596
Down-regulation Expression COX2 hsa4513
Down-regulation Expression IL1B hsa3553
In Vitro Model HeLa Human papillomavirus-related cervical adenocarcinoma Homo sapiens (Human) CVCL_0030
Result The results suggest that eugenol exerts its anticancer activities via apoptosis induction and anti-inflammatory properties and also provide the first evidence demonstrating synergism between eugenol and gemcitabine, which may enhance The therapeutic index of prevention and/or treatment of cervical cancer.
Combination Pair ID: 582
Ref_28
Pair Name Eriocalyxin B, Gemcitabine
Partner Name Eriocalyxin B
Disease Info [ICD-11: 2C10] Pancreatic cancer Investigative
Biological Phenomena Induction-->Apoptosis
Gene Regulation Down-regulation Phosphorylation AKT1 hsa207
Up-regulation Cleavage CASP3 hsa836
Up-regulation Phosphorylation MAPK8 hsa5599
Down-regulation Phosphorylation NFKB1 hsa4790
Up-regulation Cleavage PARP1 hsa142
Down-regulation Phosphorylation PDK1 hsa5163
In Vitro Model PANC-1 Pancreatic ductal adenocarcinoma Homo sapiens (Human) CVCL_0480
SW1990 Pancreatic adenocarcinoma Homo sapiens (Human) CVCL_1723
Capan-1 Pancreatic ductal adenocarcinoma Homo sapiens (Human) CVCL_0237
Capan-2 Pancreatic ductal adenocarcinoma Homo sapiens (Human) CVCL_0026
Result Gem and EriB (or Isodon extract) taken together in combination regulated PDK1/AKT1/caspase and JNK signaling and promoted apoptosis synergistically, which may contribute to the much increased anti-proliferative activity compared to either agent alone.
Combination Pair ID: 730
Ref_29
Pair Name Emodin, Gemcitabine
Partner Name Emodin
Disease Info [ICD-11: 2C10] Pancreatic cancer Investigative
Biological Phenomena Induction-->Apoptosis
Gene Regulation Down-regulation Expression CDH13 hsa1012
Down-regulation Expression NFKB1 hsa4790
Down-regulation Expression XIAP hsa331
In Vitro Model SW1990 Pancreatic adenocarcinoma Homo sapiens (Human) CVCL_1723
Result This study suggests that emodin enhances the antitumor effect of gemcitabine in SW1990 pancreatic cancer in vitro and in vivo, which may be via the downregulation of NF-κB expression, thus inhibiting the expression of XIAP.
Combination Pair ID: 271
Ref_30
Pair Name Deoxyelephantopin, Gemcitabine
Partner Name Deoxyelephantopin
Disease Info [ICD-11: 2C10] Pancreatic cancer Investigative
Biological Phenomena Induced-->Oxidative Stress
Gene Regulation Down-regulation Expression NFKB1 hsa4790
In Vitro Model BxPC-3 Pancreatic ductal adenocarcinoma Homo sapiens (Human) CVCL_0186
CFPAC-1 Cystic fibrosis Homo sapiens (Human) CVCL_1119
In Vivo Model To confirm the inhibition of tumor growth by DET and GEM, 100 μL of BxPC-3 cell suspension (5×10⁷ cells/mL) was administered subcutaneously into the right middle armpit of mice to establish subcutaneous tumors.
Result It is possible that DET could be developed as a single agent or combined with conventional chemotherapy drugs to improve the treatment of pancreatic cancer.
Combination Pair ID: 792
Ref_31
Pair Name Bufalin, Gemcitabine
Partner Name Bufalin
Disease Info [ICD-11: 2C10.0] Pancreatic ductal adenocarcinoma Investigative
Biological Phenomena Induction-->Apoptosis
Gene Regulation Up-regulation Expression MAP3K5 hsa4217
In Vitro Model BxPC-3 Pancreatic ductal adenocarcinoma Homo sapiens (Human) CVCL_0186
MIA PaCa-2 Pancreatic ductal adenocarcinoma Homo sapiens (Human) CVCL_0428
PANC-1 Pancreatic ductal adenocarcinoma Homo sapiens (Human) CVCL_0480
In Vivo Model To establish xenograft model, each mouse was subcutaneously injected with 6×10⁶ Mia PaCa-2 cells in the back.
Result These results suggest that bufalin may be a potential chemotherapeutic agent for pancreatic cancer, which could enhance the antitumor efficacy of gemcitabine when used in combination, possibly through the activation of ASK1/JNK.
Combination Pair ID: 251
Ref_32
Pair Name Bruceine D, Gemcitabine
Partner Name Bruceine D
Disease Info [ICD-11: 2C10.0] Pancreatic ductal adenocarcinoma Investigative
Biological Phenomena Inhibition-->Cell proliferation
Gene Regulation Down-regulation Expression ABCC1 hsa4363
Down-regulation Expression ABCC5 KEGG ID N.A.
Down-regulation Expression AKR1B10 KEGG ID N.A.
Down-regulation Expression HMOX1 hsa3162
Down-regulation Expression KEAP1 hsa9817
Down-regulation Expression NFE2L2 hsa4780
Down-regulation Expression NQO1 hsa1728
In Vitro Model PANC-1 Pancreatic ductal adenocarcinoma Homo sapiens (Human) CVCL_0480
Capan-2 Pancreatic ductal adenocarcinoma Homo sapiens (Human) CVCL_0026
MIA PaCa-2 Pancreatic ductal adenocarcinoma Homo sapiens (Human) CVCL_0428
In Vivo Model Capan-2, control non-specific shRNA (shControl) or Nrf2-targeting shRNA (shNrf2)-transfected Miapaca-2 cells (1.5×10⁶ cells/100 μL) were injected into the pancreatic tail of each nude mouse.
Result Our experimental findings indicate that BD, a potent Nrf2 inhibitor, holds promise for further development into a novel adjuvant therapy for PDAC.
Combination Pair ID: 1010
Ref_33
Pair Name Betulinic Acid, Gemcitabine
Partner Name Betulinic Acid
Disease Info [ICD-11: 2A00-2F9Z] Solid tumour or cancer Investigative
Gene Regulation Down-regulation Phosphorylation CHEK1 hsa1111
Down-regulation Phosphorylation RPA2 KEGG ID N.A.
In Vitro Model BxPC-3 Pancreatic ductal adenocarcinoma Homo sapiens (Human) CVCL_0186
NCI-H1299 Lung large cell carcinoma Homo sapiens (Human) CVCL_0060
HEK293T Healthy Homo sapiens (Human) CVCL_0063
In Vivo Model To establish tumor xenograft, exponentially growing mCherry-BxPC-3 cells were mixed at a 2:1 ratio with Matrigel (Becton Dickinson, Bedford, MA) and a 200 μL suspension containing 5×10⁶ cells was subcutaneously inoculated into the right flank of each mouse.
Result These data provide evidence that betulinic acid is a potential candidate for chemosensitization as a naturally occurring Chk1 inhibitor and warrants further preclinical evaluation.
Combination Pair ID: 348
Ref_34
Pair Name Beta-Sitosterol, Gemcitabine
Partner Name Beta-Sitosterol
Disease Info [ICD-11: 2C10] Pancreatic cancer Investigative
Biological Phenomena Induction-->Blockade of cell cycle in G0/G1 phase
Gene Regulation Down-regulation Phosphorylation AKT1 hsa207
Up-regulation Expression BAX hsa581
Down-regulation Expression BCL2 hsa596
Up-regulation Expression CDH1 hsa999
Down-regulation Phosphorylation GSK3B hsa2932
Down-regulation Phosphorylation NFKB1 hsa4790
Down-regulation Expression SNAI1 hsa6615
Down-regulation Expression VIM hsa7431
In Vitro Model MIA PaCa-2 Pancreatic ductal adenocarcinoma Homo sapiens (Human) CVCL_0428
BxPC-3 Pancreatic ductal adenocarcinoma Homo sapiens (Human) CVCL_0186
In Vivo Model BXPC-3 cells (0.2 mL; 7×10⁶ cells) were subcutaneously injected into the right flank of the nude mice.
Result β-Sitosterol and Gemcitabine Exhibit Synergistic Anti-pancreatic Cancer Activity by Modulating Apoptosis and Inhibiting Epithelial-Mesenchymal Transition by Deactivating Akt/GSK-3β Signaling
Combination Pair ID: 440
Ref_35
Pair Name alpha-Mangostin, Gemcitabine
Partner Name alpha-Mangostin
Disease Info [ICD-11: 2C13] Gallbladder cancer Investigative
Biological Phenomena Induction-->Apoptosis
Gene Regulation Down-regulation Expression ACACA hsa31
Up-regulation Expression BAX hsa581
Down-regulation Expression BCL2 hsa596
Down-regulation Expression FASN hsa2194
Down-regulation Expression PCNA hsa5111
Up-regulation Phosphorylation PRKAA1 hsa5562
Down-regulation Expression SREBF1 hsa6720
In Vitro Model GBC-SD Gallbladder carcinoma Homo sapiens (Human) CVCL_6903
NOZ Gallbladder carcinoma Homo sapiens (Human) CVCL_3079
Result α-Mangostin suppresses the de novo lipogenesis and enhances the chemotherapeutic response to gemcitabine in gallbladder carcinoma cells via targeting the AMPK/SREBP1 cascades.
Reversing Drug Resistance
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Combination Pair ID: 1035
Ref_36
Pair Name Shikonin, Gemcitabine
Partner Name Shikonin
Disease Info [ICD-11: 2C10] Pancreatic cancer Investigative
Biological Phenomena Inhibition-->Glycolysis
Gene Regulation Down-regulation Expression HK2 hsa3099
Down-regulation Expression LDHA hsa3939
Down-regulation Expression MMP2 hsa4313
Down-regulation Expression PDK1 hsa5163
Down-regulation Expression SLC16A4 hsa9122
Down-regulation Expression SLC2A1 hsa6513
Down-regulation Expression VIM hsa7431
In Vitro Model WI-38 Healthy Homo sapiens (Human) CVCL_0579
PANC-1 Pancreatic ductal adenocarcinoma Homo sapiens (Human) CVCL_0480
In Vivo Model Female BALB/c mice (18-22 g, 6-week-old) were injected subcutaneously into the left flank with PANC-1 cells (1×10⁶ cells/mouse) or PANC-1 cells and CAFs (2:1, 1×10⁶ cells, 5×105 cells/mouse).
Result These results indicate that shikonin reduced MCT4 expression and activation, resulting in inhibition of aerobic glycolysis in CAFs and overcoming CAF-induced gemcitabine resistance in PC. Shikonin is a promising chemosensitizing phytochemical agent when used in combination with gemcitabine for PC treatment. The results suggest that disrupting the metabolic coupling between cancer cells and stromal cells might provide an attractive strategy for improving gemcitabine efficacy.
Combination Pair ID: 498
Ref_37
Pair Name Isocorydine, Gemcitabine
Partner Name Isocorydine
Disease Info [ICD-11: 2C10] Pancreatic cancer Investigative
Biological Phenomena Inhibition-->Epithelial-mesenchymal transition
Gene Regulation Up-regulation Expression CDH1 hsa999
Down-regulation Expression CDH2 hsa1000
Down-regulation Expression SNAI1 hsa6615
Down-regulation Phosphorylation STAT3 hsa6774
Down-regulation Expression TWIST1 hsa7291
Down-regulation Expression VIM hsa7431
In Vitro Model CFPAC-1 Cystic fibrosis Homo sapiens (Human) CVCL_1119
PANC-1 Pancreatic ductal adenocarcinoma Homo sapiens (Human) CVCL_0480
PaTu 8988t Pancreatic adenocarcinoma Homo sapiens (Human) CVCL_1847
In Vivo Model 1×10⁷ PANC-1 cells were suspended in 100 μL of phosphate-buffered saline (PBS) and implanted subcutaneously into the right flank of each nude mouse.
Result The synergistic treatment effect of the combination treatment of ICD and gemcitabine in pancreatic cancer cells was confirmed in established xenograft models.
Combination Pair ID: 877
Ref_38
Pair Name Gossypol, Gemcitabine
Partner Name Gossypol
Disease Info [ICD-11: 2A00-2F9Z] Solid tumour or cancer Investigative
Biological Phenomena Induction-->Apoptosis
Gene Regulation Down-regulation Expression BCL2 hsa596
Down-regulation Expression BCL-xL hsa598
Up-regulation Expression MCL1 hsa4170
Up-regulation Expression PMAIP1 hsa5366
In Vitro Model CNE-1 Nasopharyngeal carcinoma Homo sapiens (Human) CVCL_6888
YCC-16 Gastric adenocarcinoma Homo sapiens (Human) CVCL_9649
MCF-7 Invasive breast carcinoma of no special type Homo sapiens (Human) CVCL_0031
Result Combination therapy with gossypol reveals synergism against gemcitabine resistance in cancer cells with high BCL-2 expression
Combination Pair ID: 386
Ref_39
Pair Name Curcumin, Gemcitabine
Partner Name Curcumin
Disease Info [ICD-11: 2C25] Lung cancer Investigative
Biological Phenomena Inhibition-->Epithelial-mesenchymal transition
Gene Regulation Up-regulation Expression CDH1 hsa999
Down-regulation Expression CDH2 hsa1000
Down-regulation Expression MMP9 hsa4318
Down-regulation Expression VIM hsa7431
In Vitro Model A-549 Lung adenocarcinoma Homo sapiens (Human) CVCL_0023
In Vivo Model A549/GEM resistant cells were collected and resuspended with PBS and injected into the tail veins of nude mice. For each mouse, 1×10⁶ cells in 150 μL of PBS were injected.
Result Cur reversed GEM resistance and inhibited the EMT process in A549/GEM cells. GEM, combined with Cur, is safe and more effective in the treatment of non-small cell lung cancer.
Combination Pair ID: 178
Ref_40
Pair Name Brusatol, Gemcitabine
Partner Name Brusatol
Disease Info [ICD-11: 2C10] Pancreatic cancer Investigative
Biological Phenomena Induction-->Apoptosis
Gene Regulation Down-regulation Expression ABCB1 hsa5243
Down-regulation Expression ABCC1 hsa4363
Down-regulation Expression ABCC2 hsa1244
Down-regulation Expression ABCC3 hsa8714
Down-regulation Expression ABCC4 KEGG ID N.A.
Down-regulation Expression ABCC5 KEGG ID N.A.
Down-regulation Expression ABCC5 KEGG ID N.A.
Down-regulation Expression HMOX1 hsa3162
Down-regulation Expression NFE2L2 hsa4780
Down-regulation Expression NQO1 hsa1728
Up-regulation Expression ROS1 hsa6098
In Vitro Model PANC-1 Pancreatic ductal adenocarcinoma Homo sapiens (Human) CVCL_0480
BxPC-3 Pancreatic ductal adenocarcinoma Homo sapiens (Human) CVCL_0186
PaTu 8988s Pancreatic adenocarcinoma Homo sapiens (Human) CVCL_1846
In Vivo Model PANC-1 cells (4×10⁶) were resuspended in 100 μL PBS and then subcutaneously injected in the right flank of nude mice.
Result Our results suggest that brusatol is capable of enhancing the antitumour effects of gemcitabine in both pancreatic cancer cells and PANC-1 xenografts via suppressing the Nrf2 pathway.
03. Reference
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