Pair Name	Amentoflavone, Sorafenib
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.

Pair Name	Amentoflavone, Sorafenib
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.

Pair Name	Amentoflavone, Sorafenib
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.