Pair Name	Beta-Elemene, Erlotinib
Partner Name	Erlotinib
Disease Info	[ICD-11: 2C25]	Lung cancer		Investigative
Biological Phenomena	Induction-->Ferroptosis
Gene Regulation	Up-regulation	Expression	H19	KEGG ID N.A.
In Vitro Model	NCI-H1975	Lung adenocarcinoma	Homo sapiens (Human)	CVCL_1511
	NCI-H1650	Minimally invasive lung adenocarcinoma	Homo sapiens (Human)	CVCL_1483
	NCI-H1819	Lung adenocarcinoma	Homo sapiens (Human)	CVCL_1497
In Vivo Model	5×10⁶ H1975 shRNA-NC cells or H1975 H19-shRNA cells were injected subcutaneously into 6-week-old female nude mice in the right flanks.
Result	Our data showed that β-elemene combined with erlotinib could enhance sensitivity to EGFR-TKIs through induction of ferroptosis via H19 in primary EGFR-TKI-resistant lung cancer, providing a promising strategy to overcome EGFR-TKI resistance in NSCLC patients.

Pair Name	Beta-Elemene, Bevacizumab
Partner Name	Bevacizumab
Disease Info	[ICD-11: 2B90]	Colon cancer		Investigative
Biological Phenomena	Induction-->Apoptosis
Gene Regulation	Down-regulation	Expression	BCL2	hsa596
	Down-regulation	Expression	MKI67	hsa4288
	Down-regulation	Expression	PECAM1	hsa5175
	Down-regulation	Expression	VEGFA	hsa7422
In Vitro Model	HCT 116	Colon carcinoma	Homo sapiens (Human)	CVCL_0291
In Vivo Model	HCT-116 cells in the logarithmic growth phase were selected and suspended in PBS after 0.25% pancreatic enzyme digestion (cell concentration: 1×10⁷/mL, living cells >95% after trypan blue staining). Nude mice were intraperitoneally injected with 0.2 mL of the cell suspension (total, 2×106 cells/mice) in the right axilla.
Result	Bevacizumab exerts a synergistic effect with β-elemene in suppressing the growth of tumors derived from HCT-116 cells, and the related mechanisms may include the inhibition of tumor cell proliferation and tumor angiogenesis and the promotion of tumor cell apoptosis.

Pair Name	Beta-Elemene, Fluorouracil
Partner Name	Fluorouracil
Disease Info	[ICD-11: 2C60]	Breast cancer		Investigative
Gene Regulation	Down-regulation	Phosphorylation	AKT1	hsa207
	Down-regulation	Expression	CD40	hsa958
	Down-regulation	Expression	CHUK	hsa1147
	Down-regulation	Expression	IKBKB	hsa3551
	Down-regulation	Phosphorylation	MAPK1	hsa5594
	Down-regulation	Phosphorylation	PDK1	hsa5163
	Down-regulation	Expression	PIK3CA	hsa5290
	Down-regulation	Expression	PIK3CA	hsa5290
	Down-regulation	Expression	PIK3R1	hsa5295
	Down-regulation	Phosphorylation	RAF1	hsa5894
	Down-regulation	Expression	RELA	hsa5970
In Vitro Model	MDA-MB-231	Breast adenocarcinoma	Homo sapiens (Human)	CVCL_0062
	BT-549	Invasive breast carcinoma of no special type	Homo sapiens (Human)	CVCL_1092
In Vivo Model	MDA-MB-231 cells (5×10⁶ cells in 100 µL of PBS) were subcutaneously injected to the left flank of each mouse.
Result	The conclusion obtained, considering that the results suggest that the combination may be important specifically in the treatment of TNBC.

Pair Name	Beta-Elemene, Cetuximab
Partner Name	Cetuximab
Disease Info	[ICD-11: 2B91]	Colorectal cancer		Investigative
Biological Phenomena	Induction-->Ferroptosis
Gene Regulation	Up-regulation	Expression	CDH1	hsa999
	Down-regulation	Expression	CDH2	hsa1000
	Down-regulation	Expression	FTH1	hsa2495
	Down-regulation	Expression	GLS	hsa2744
	Down-regulation	Expression	GPX4	hsa2879
	Up-regulation	Expression	HMOX1	hsa3162
	Down-regulation	Expression	MMP9	hsa4318
	Down-regulation	Expression	SLC40A1	KEGG ID N.A.
	Down-regulation	Expression	SLC7A11	hsa23657
	Down-regulation	Expression	SNAI1	hsa6615
	Down-regulation	Expression	SNAI2	hsa6591
	Up-regulation	Expression	TF	KEGG ID N.A.
	Down-regulation	Expression	VIM	hsa7431
In Vitro Model	HCT 116	Colon carcinoma	Homo sapiens (Human)	CVCL_0291
	LoVo	Colon adenocarcinoma	Homo sapiens (Human)	CVCL_0399
In Vivo Model	HCT116-luc cells were digested and washed by cold PBS for three times, and the final concentration was 2.5×10⁶/ml in cold PBS. A volume of 100 μl cell suspension was injected subcutaneously into right dorsal flank of mice.
Result	natural product β-elemene is a new ferroptosis inducer and combinative treatment of β-elemene and cetuximab is sensitive to KRAS mutant CRC cells by inducing ferroptosis and inhibiting EMT, which will hopefully provide a prospective strategy for CRC patients with RAS mutations.

Pair Name	Beta-Elemene, Cabazitaxel
Partner Name	Cabazitaxel
Disease Info	[ICD-11: 2A00]	Glioblastoma multiforme		Investigative
Gene Regulation	Up-regulation	Expression	ATP1A1	hsa476
In Vitro Model	RG2	Invasive breast carcinoma of no special type	Homo sapiens (Human)	CVCL_1092
In Vivo Model	Approximately 2.5×10⁷ glioma-luc cells in medium were injected slowly into the brain right striatum of nude mice (bright lateral: 2.0 mm, bregma: 1.8 mm, depth: 3.5 mm).
Result	These findings indicate that the active-targeting biomimetic liposome, Tf-ELE/CTX@BLIP, is a promising nanoplatform for delivery of drugs to gliomas.

Pair Name	Beta-Elemene, Bortezomib
Partner Name	Bortezomib
Disease Info	[ICD-11: 2C10]	Pancreatic cancer		Investigative
Biological Phenomena	Induction-->Blockade of cell cycle in G2/M phase
Gene Regulation	Up-regulation	Cleavage	CASP3	hsa836
	Down-regulation	Expression	CCNB1	hsa891
	Up-regulation	Expression	CDKN1A	hsa1026
	Down-regulation	Expression	NFKBIA	hsa4792
	Down-regulation	Expression	RELA	hsa5970
	Down-regulation	Expression	TP53	hsa7157
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	Bortezomib or elemene alone inhibited the tumor growth to a certain extent, while the combination treatment significantly enhanced the antitumor activity relative to bortezomib alone assessed by tumor growth curve and endpoint tumor weight, suggesting that elemene boosts bortezomib’s anti-pancreatic cancer activity, and their combination displays significant antitumor efficacy with no obvious systematic toxicity.
Result	Elemene sensitizes pancreatic cancer cells to bortezomib by enhancing proteasome inhibition via molecular patch mechanism

Pair Name	Beta-Elemene, Cisplatin
Partner Name	Cisplatin
Disease Info	[ICD-11: 2C25]	Lung cancer		Investigative
Biological Phenomena	Induction-->Apoptosis
Gene Regulation	Up-regulation	Expression	BAD	hsa572
	Down-regulation	Expression	BCL2	hsa596
	Up-regulation	Expression	CASP3	hsa836
In Vitro Model	A-549	Lung adenocarcinoma	Homo sapiens (Human)	CVCL_0023
Result	These results define a pathway of procaspase‑3-β-ELE function that involves decreased mitochondrial membrane potential, leading to apoptosis triggered by the release of cytochrome c into the cytoplasm and the modulation of apoptosis-related genes. The reversal of drug resistance of the A549/DDP cell line by β-ELE may be derived from its effect in inducing apoptosis.

Pair Name	Beta-Elemene, Cisplatin
Partner Name	Cisplatin
Disease Info	[ICD-11: 2C25]	Lung 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	CASP7	hsa840
	Up-regulation	Cleavage	CASP9	hsa842
	Down-regulation	Expression	XIAP	hsa331
In Vitro Model	NCI-H460	Lung large cell carcinoma	Homo sapiens (Human)	CVCL_0459
	A-549	Lung adenocarcinoma	Homo sapiens (Human)	CVCL_0023
Result	Our data provide a rationale for developing a combination of beta-elemene and cisplatin as a regimen for the treatment of lung carcinoma and other cisplatin-resistant tumors.

Pair Name	Beta-Elemene, Cisplatin
Partner Name	Cisplatin
Disease Info	[ICD-11: 2C94]	Bladder 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	Cleavage	PARP1	hsa142
	Up-regulation	Phosphorylation	PRKAA1	hsa5562
In Vitro Model	T24	Bladder carcinoma	Homo sapiens (Human)	CVCL_0554
	5637	Bladder carcinoma	Homo sapiens (Human)	CVCL_0126
Result	The results of the present study suggested that β-ELE inhibited the proliferation of bladder cancer cells in vitro and enhanced cisplatin-induced mitochondria-dependent apoptosis via the ROS-AMPK signaling pathway. Combination therapy with β-ELE requires further investigation as a potential treatment of bladder cancer.

Pair Name	Beta-Elemene, Cisplatin
Partner Name	Cisplatin
Disease Info	[ICD-11: 2C82]	Prostate cancer		Investigative
Biological Phenomena	Induction-->Apoptosis
Gene Regulation	Down-regulation	Expression	BCL2	hsa596
	Down-regulation	Expression	BCL-xL	hsa598
	Up-regulation	Cleavage	CASP3	hsa836
	Up-regulation	Cleavage	CASP9	hsa842
In Vitro Model	DU145	Prostate carcinoma	Homo sapiens (Human)	CVCL_0105
	PC-3	Prostate carcinoma	Homo sapiens (Human)	CVCL_0035
Result	β-elemene enhancement of cisplatin-induced apoptosis via mitochondrial activation of the caspase-mediated apoptotic pathway may account for the augmented anti-cancer potency of cisplatin in prostate cancer. Cisplatin combined with β-elemene as a chemosensitizer or adjuvant warrants further study and may be potentially useful as a first-line treatment of androgen-independent prostate carcinomas.

Pair Name	Beta-Elemene, Cisplatin
Partner Name	Cisplatin
Disease Info	[ICD-11: 2C94]	Bladder cancer		Investigative
Biological Phenomena	Induction-->Apoptosis
Gene Regulation	Up-regulation	Activity	CASP10	hsa843
	Up-regulation	Activity	CASP3	hsa836
	Up-regulation	Activity	CASP7	hsa840
	Up-regulation	Activity	CASP8	hsa841
	Up-regulation	Activity	CASP9	hsa842
In Vitro Model	T24	Bladder carcinoma	Homo sapiens (Human)	CVCL_0554
	5637	Bladder carcinoma	Homo sapiens (Human)	CVCL_0126
Result	Cisplatin combined with β-elemene as a chemosensitizer warrants further pre-clinical therapeutic studies and may be useful for the treatment of cisplatin-resistant bladder cancer and other types of carcinomas.

Pair Name	Beta-Elemene, Cisplatin
Partner Name	Cisplatin
Disease Info	[ICD-11: 2C25]	Lung cancer		Investigative
Biological Phenomena	Induction-->Blockade of cell cycle in G2/M phase
Gene Regulation	Down-regulation	Expression	CCNB1	hsa891
	Up-regulation	Expression	CDKN1A	hsa1026
	Up-regulation	Expression	GADD45A	hsa1647
	Up-regulation	Expression	IFI27	hsa3429
In Vitro Model	NCI-H460	Lung large cell carcinoma	Homo sapiens (Human)	CVCL_0459
	A-549	Lung adenocarcinoma	Homo sapiens (Human)	CVCL_0023
Result	β-elemenal may have greater potential as an anticancer alternative to β-elemene in treating lung cancer and other tumors.

Pair Name	Beta-Elemene, Cisplatin
Partner Name	Cisplatin
Disease Info	[ICD-11: 2B63]	Gingival squamous cell carcinoma		Investigative
Biological Phenomena	Induction-->Apoptosis
Gene Regulation	Up-regulation	Expression	BAX	hsa581
	Down-regulation	Expression	BCL2	hsa596
	Up-regulation	Expression	CASP3	hsa836
	Down-regulation	Phosphorylation	JAK2	hsa3717
	Down-regulation	Phosphorylation	STAT3	hsa6774
In Vitro Model	YD-38	Gingival squamous cell carcinoma	Homo sapiens (Human)	CVCL_L083
Result	The results indicated that β-elemene promoted the anti-proliferative and apoptotic effect of cisplatin by inhibiting STAT3 and blocking the JAK2-STAT3 signaling pathway in GSCC in vitro and in vivo.

Pair Name	Beta-Elemene, Cisplatin
Partner Name	Cisplatin
Disease Info	[ICD-11: 2C73]	Ovarian cancer		Investigative
Biological Phenomena	Induction-->Mitochondria-mediated apoptosis
Gene Regulation	Up-regulation	Expression	BAX	hsa581
	Down-regulation	Expression	BCL2	hsa596
	Down-regulation	Expression	BCL-xL	hsa598
	Up-regulation	Expression	CASP3	hsa836
	Up-regulation	Expression	CASP8	hsa841
	Up-regulation	Cleavage	CASP9	hsa842
In Vitro Model	A2780/CP70	Ovarian endometrioid adenocarcinoma	Homo sapiens (Human)	CVCL_0135
	MCAS	Ovarian mucinous cystadenocarcinoma	Homo sapiens (Human)	CVCL_3020
Result	These data indicate that β-elemene sensitizes chemoresistant ovarian carcinoma cells to cisplatin-induced apoptosis and that the augmented effect of β-elemene on cisplatin cytotoxicity and sensitivity in resistant ovarian tumor cells is mediated through a mitochondria- and caspase-dependent cell death pathway.

Pair Name	Beta-Elemene, Temozolomide
Partner Name	Temozolomide
Disease Info	[ICD-11: 2A00]	Glioblastoma multiforme		Investigative
Gene Regulation	Down-regulation	Expression	AKT1	hsa207
	Down-regulation	Phosphorylation	ATM	hsa472
	Down-regulation	Expression	H2AX	hsa3014
	Down-regulation	Expression	MAPK3	hsa5595
In Vitro Model	U-87MG ATCC	Glioblastoma	Homo sapiens (Human)	CVCL_0022
	T98G	Glioblastoma	Homo sapiens (Human)	CVCL_0556
	U-251MG	Astrocytoma	Homo sapiens (Human)	CVCL_0021
	LN-229	Glioblastoma	Homo sapiens (Human)	CVCL_0393
	C6	Rat malignant glioma	Rattus norvegicus (Rat)	CVCL_0194
Result	These results revealed that β-elemene could significantly increase the radiosensitivity and chemosensitivity of GBM. β-elemene may be used as a potential drug in combination with the radiotherapy and chemotherapy of GBM

Pair Name	Beta-Elemene, Gefitinib
Partner Name	Gefitinib
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
	Up-regulation	Expression	HES1	hsa3280
	Up-regulation	Expression	MYC	hsa4609
	Up-regulation	Expression	NOTCH1	hsa4851
	Up-regulation	Expression	SHH	hsa6469
	Down-regulation	Expression	SNAI1	hsa6615
	Up-regulation	Expression	SOX2	hsa6657
	Down-regulation	Expression	TWIST1	hsa7291
	Down-regulation	Expression	VIM	hsa7431
	Down-regulation	Expression	ZEB1	hsa6935
In Vitro Model	A-549	Lung adenocarcinoma	Homo sapiens (Human)	CVCL_0023
	NCI-H1299	Lung large cell carcinoma	Homo sapiens (Human)	CVCL_0060
Result	The findings may have potential implications for treating aggressive and resistant lung cancers.

Pair Name	Beta-Elemene, TNF-related apoptosis inducing ligand
Partner Name	TNF-related apoptosis inducing ligand
Disease Info	[ICD-11: 2C25]	Lung cancer		Investigative
Biological Phenomena	Induction-->Apoptosis
Gene Regulation	Up-regulation	Expression	CASP3	hsa836
	Up-regulation	Expression	CASP8	hsa841
	Up-regulation	Expression	FADD	hsa8772
	Up-regulation	Expression	PARP1	hsa142
	Up-regulation	Expression	TNFRSF10B	hsa8795
In Vitro Model	BGC-823	Human papillomavirus-related cervical adenocarcinoma	Homo sapiens (Human)	CVCL_3360
	SGC-7901	Human papillomavirus-related cervical adenocarcinoma	Homo sapiens (Human)	CVCL_0520
Result	Our results suggest that β-elemene increases the sensitivity of gastric cancer cells to TRAIL partially by promoting the formation of DISC in lipid rafts.

Pair Name	Beta-Elemene, Rapamycin
Partner Name	Rapamycin
Disease Info	[ICD-11: 2A83]	Multiple myeloma		Investigative
Gene Regulation	Down-regulation	Phosphorylation	AKT1	hsa207
In Vitro Model	FTC-133	Thyroid gland follicular carcinoma	Homo sapiens (Human)	CVCL_1219
Result	We demonstrate that the novel combination of mTOR inhibitor with β-elemene synergistically attenuates tumor cell growth in follicular thyroid cancer, which requires additional preclinical validation.

Pair Name	Beta-Elemene, Etoposide
Partner Name	Etoposide
Disease Info	[ICD-11: 2C25]	Lung cancer		Investigative
Biological Phenomena	Induction-->Apoptosis
Gene Regulation	Up-regulation	Expression	BAX	hsa581
	Down-regulation	Expression	CCND1	hsa595
	Up-regulation	Expression	CDKN1A	hsa1026
	Up-regulation	Cleavage	PARP1	hsa142
	Up-regulation	Expression	TP53	hsa7157
In Vitro Model	A-549	Lung adenocarcinoma	Homo sapiens (Human)	CVCL_0023
Result	These results suggest that the combination of β-elemene and VP-16 may be a promising therapeutic option for lung cancer.

Pair Name	Beta-Elemene, Oxaliplatin
Partner Name	Oxaliplatin
Disease Info	[ICD-11: 2B91]	Colorectal cancer		Investigative
Biological Phenomena	Induction-->Cellular uptake
Gene Regulation	Down-regulation	Phosphorylation	AKT1	hsa207
	Up-regulation	Expression	BECN1	hsa8678
	Up-regulation	Cleavage	CASP3	hsa836
	Up-regulation	Expression	MAP1LC3A	hsa84557
	Down-regulation	Phosphorylation	MAPK3	hsa5595
	Up-regulation	Cleavage	PAEP	hsa5047
In Vitro Model	MHCC97-H	Adult hepatocellular carcinoma	Homo sapiens (Human)	CVCL_4972
	HCCLM3	Adult hepatocellular carcinoma	Homo sapiens (Human)	CVCL_6832
In Vivo Model	Human HCC cell line MHCC97H were used to estabolish xenograft models in the BALB/c mice.
Result	Our findings show that β-elemene can block the reduction of CTR1 resulting from oxaliplatin treatment, and therefore has a synergistic anti-HCC effect with oxaliplatin by enhancing cellular uptake of oxaliplatin. The synergistic effects of β-elemene and oxaliplatin deserve further evaluation in clinical settings.