Pair Name	Shogaol, Fluorouracil
Partner Name	Fluorouracil
Disease Info	[ICD-11: 2C12]	Hepatocellular carcinoma		Investigative
Biological Phenomena	Induction-->Blockade of cell cycle in G0/G1 phase
Gene Regulation	Down-regulation	Expression	ABCC1	hsa4363
	Down-regulation	Phosphorylation	AKT1	hsa207
	Down-regulation	Expression	CCNA2	hsa890
	Down-regulation	Expression	CCND1	hsa595
	Down-regulation	Expression	CCNE1	hsa898
	Down-regulation	Phosphorylation	MTOR	hsa2475
In Vivo Model	2×10⁶ HepG2 cells/mouse were suspended in serum-free DMEM (200 μL) and then subcutaneously inoculated into the right flank of the mice.
Result	Influence of 6-shogaol potentiated on 5-fluorouracil treatment of liver cancer by promoting apoptosis and cell cycle arrest by regulating AKT/mTOR/MRP1 signalling

Pair Name	Shogaol, Gefitinib
Partner Name	Gefitinib
Disease Info	[ICD-11: 2C73]	Ovarian Cancer		Investigative
Biological Phenomena	Induction-->Endoplasmic reticulum stress
Gene Regulation	Up-regulation	Expression	ATF4	hsa468
	Up-regulation	Cleavage	CASP3	hsa836
	Up-regulation	Cleavage	CASP8	hsa841
	Up-regulation	Cleavage	CASP9	hsa842
	Up-regulation	Expression	CD63	hsa967
	Up-regulation	Expression	CDH1	hsa999
	Down-regulation	Expression	CDH2	hsa1000
	Up-regulation	Expression	DDIT3	hsa1649
	Up-regulation	Phosphorylation	EIF2AK3	hsa9451
	Up-regulation	Phosphorylation	EIF2S1	hsa1965
	Up-regulation	Expression	HSPA5	hsa3309
	Up-regulation	Expression	NOX4	hsa50507
	Down-regulation	Expression	SNAI1	hsa6615
	Down-regulation	Expression	SNAI2	hsa6591
	Up-regulation	Expression	TNFRSF10B	hsa8795
	Down-regulation	Expression	VIM	hsa7431
In Vitro Model	A2780	Ovarian endometrioid adenocarcinoma	Homo sapiens (Human)	CVCL_0134
	OVCAR-3	High grade ovarian serous adenocarcinoma	Homo sapiens (Human)	CVCL_0465
	Caov-3	High grade ovarian serous adenocarcinoma	Homo sapiens (Human)	CVCL_0201
	SK-OV-3	Ovarian serous cystadenocarcinoma	Homo sapiens (Human)	CVCL_0532
In Vivo Model	For the mice xenograft experiment, mice, aged six weeks, were inoculated with an A2780 human ovarian cancer cell line by subcutaneously (sc) implanting 1×10⁷ cultured cells into the right thigh.
Result	Our results suggest that 6-shogaol exerts a potential anti-cancer effect in ovarian cancer and combination treatment with 6-shogaol and gefitinib may provide a novel anti-tumor therapeutic strategy in gefitinib-resistant ovarian cancer.

Pair Name	Shogaol, Methotrexate
Partner Name	Methotrexate
Disease Info	[ICD-11: 2B33.3]	Acute lymphoblastic leukemia		Investigative
Biological Phenomena	Induction-->ROS generation
Gene Regulation	Up-regulation	Expression	BBC3	hsa27113
	Up-regulation	Expression	CDKN1A	hsa1026
	Down-regulation	Expression	FASN	hsa2194
	Up-regulation	Expression	TP53	hsa7157
In Vivo Model	Four‐ to six‐week‐old female athymic nude mice (C57BL/6 nude) were injected with 1.5×10⁷ CCRF‐CEM cells in 100 μL FBS, subcutaneously. In order to confirm leukaemia engraftment, flow cytometry was performed on mice blood samples by using antibodies against CCRF‐CEM cell‐line CD markers.
Result	The current study revealed the in vivo novel anti-leukaemic role of ginger extract, promoted by MTX. Moreover, 6-shogaol was introduced as the major player of ginger cytotoxicity through inducing p53 activity and ROS generation.

Pair Name	Shogaol, Fluorouracil
Partner Name	Fluorouracil
Disease Info	[ICD-11: 2B90]	Colon cancer		Investigative
Biological Phenomena	Induction-->Autophagy
Gene Regulation	Up-regulation	Expression	ATG7	hsa10533
	Up-regulation	Expression	BAX	hsa581
	Up-regulation	Expression	BECN1	hsa8678
	Up-regulation	Expression	CASP3	hsa836
In Vitro Model	SW480	Colon adenocarcinoma	Homo sapiens (Human)	CVCL_0546
	SW620	Colon adenocarcinoma	Homo sapiens (Human)	CVCL_0547
Result	Our data suggest that the addition of 6-shogaol to established chemotherapeutic regimens could potentially be a remarkable therapeutic strategy for colorectal cancer.

Pair Name	Shogaol, Gemcitabine
Partner Name	Gemcitabine
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.

Pair Name	Shogaol, TNF-related apoptosis inducing ligand
Partner Name	TNF-related apoptosis inducing ligand
Disease Info	[ICD-11: 2B90]	Colon cancer		Investigative
Biological Phenomena	Induction-->Apoptosis
Gene Regulation	Up-regulation	Expression	BAX	hsa581
	Down-regulation	Expression	BCL2	hsa596
	Down-regulation	Expression	BIRC5	hsa332
	Up-regulation	Cleavage	CASP3	hsa836
	Up-regulation	Cleavage	CASP8	hsa841
	Up-regulation	Phosphorylation	MAPK1	hsa5594
	Up-regulation	Phosphorylation	MAPK8	hsa5599
	Up-regulation	Cleavage	PARP1	hsa142
	Up-regulation	Expression	TNFRSF10B	hsa8795
In Vitro Model	HCT 116	Colon carcinoma	Homo sapiens (Human)	CVCL_0291
	Caco-2	Colon adenocarcinoma	Homo sapiens (Human)	CVCL_0025
	SW620	Colon adenocarcinoma	Homo sapiens (Human)	CVCL_0547
Result	This study gives rise to the possibility of applying shogaol as an antitumor agent that can be used for the purpose of combination treatment with TRAIL in TRAIL-resistant colon tumor therapy.