Pair Name	Polyphyllin I, Cisplatin
Partner Name	Cisplatin
Disease Info	[ICD-11: 2C25]	Lung cancer		Investigative
Biological Phenomena	Induction-->Apoptosis
Gene Regulation	Down-regulation	Expression	AKT1	hsa207
	Up-regulation	Expression	BAX	hsa581
	Down-regulation	Expression	BCL2	hsa596
	Up-regulation	Cleavage	CASP3	hsa836
	Up-regulation	Expression	CDH1	hsa999
	Down-regulation	Expression	CIP2A	hsa57650
	Up-regulation	Expression	MTOR	hsa2475
	Up-regulation	Cleavage	PARP1	hsa142
	Down-regulation	Expression	TP53	hsa7157
	Down-regulation	Expression	VIM	hsa7431
In Vitro Model	A-549/DDP	Lung adenocarcinoma	Homo sapiens (Human)	CVCL_0023
Result	The results from the present study demonstrated that PPI and PPVII may function as chemosensitizers by enhancing apoptosis via the p53 pathway, reversing EMT and suppressing the CIP2A/AKT/mTOR signaling axis, and the combination with DDP may be a promising strategy for the development of new therapeutic agents.

Pair Name	Polyphyllin I, Enzalutamide
Partner Name	Enzalutamide
Disease Info	[ICD-11: 2C12]	Hepatocellular carcinoma		Investigative
Gene Regulation	Down-regulation	Expression	MUC1	hsa4582
	Down-regulation	Expression	RELA	hsa5970
In Vitro Model	DU145	Prostate carcinoma	Homo sapiens (Human)	CVCL_0105
	PC-3	Prostate carcinoma	Homo sapiens (Human)	CVCL_0035
In Vivo Model	DU145 prostate cancer cells carrying the luciferase report gene (1×10⁶ cells) in 100 µL PBS were implanted via subcutaneous injection into the flanks of the mice.
Result	Our results indicate that PPI inhibits the growth of CRPC cells by inhibiting p65 protein and concomitantly reducing HOTAIR expression, thereby suppressing MUC1 gene expression. The novel regulatory interaction of p65 and HOTAIR converge in the inhibition of MUC1 expression and overall PPI response. The combination of PPI and enzalutamide exhibits synergy. This study reveals a novel mechanism underlying the synergistic inhibitory effect of PPI and enzalutamide on the growth of CRPC cells.

Pair Name	Polyphyllin I, Palbociclib
Partner Name	Palbociclib
Disease Info	[ICD-11: 2C25]	Lung cancer		Investigative
Biological Phenomena	Induction-->Apoptosis
Gene Regulation	Up-regulation	Cleavage	CASP3	hsa836
	Down-regulation	Expression	CCNE1	hsa898
	Down-regulation	Phosphorylation	CDK2	hsa1017
	Down-regulation	Phosphorylation	CDK4	hsa1019
	Down-regulation	Phosphorylation	CDK6	hsa1021
	Up-regulation	Expression	CDKN1A	hsa1026
	Down-regulation	Phosphorylation	RB1	hsa5925
In Vitro Model	A-549	Lung adenocarcinoma	Homo sapiens (Human)	CVCL_0023
	NCI-H460	Lung large cell carcinoma	Homo sapiens (Human)	CVCL_0459
In Vivo Model	A549 cells (3×10⁶) in 0.2 mL medium were injected subcutaneously into the right flank of each nude mice.
Result	We first time demonstrated PPI can disturb CDK2 function through upregulation of p21. The PPI effect on CDK2 provides a choice for a chemotherapeutic strategy for the elimination of NSCLC. Our study highlighted the clinical significance of simultaneously blocking of CDK2 and CDK4/6 for NSCLC treatment.