Pair Name	Fisetin, Sorafenib
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.

Pair Name	Fisetin, Sorafenib
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

Pair Name	Fisetin, Sorafenib
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.