Pair Name	Shikonin, Gemcitabine
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.

Pair Name	Shikonin, Gemcitabine
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.