Relationship between Smad4-independent pathway of TGF-?1 and drug-resistance of pancreatic cancer cell line / 第二军医大学学报

ABSTRACT

Objective: To investigate the relationship between the Smad4-independent pathway of TGF-?1 and drug-resistance of pancreatic cancer. Methods: The sensitivities of Smad4 homozygous-deleted pancreatic cancer cell line BxPC3 to different kinds of anti-cancer drugs (5-Fu, Gemzar, Oxaliplatin, Cisplatin, CPT-11 and Epirubicin) were observed by MTT assay before and after they were transfected with full-length cDNA of TGF-?1 or treated with TGF-?1 (5 and 10 ng/ml) solution. Western blot was used to detect p170 protein expression after stimulation with different concentrations of TGF-?1. Results: Cisplatin had the most powerful killing effect on BxPC3 cells, followed by Oxaliplatin, 5-Fu and CPT-11 with moderate effect and Gemzar and Epirubicin with the least effect. Cells transfected with full-length cDNA of TGF-?1 or treated with TGF-?1 solution became less sensitive to Cisplatin. Western blot revealed upregulation of p170 expression by TGF-?1. Conclusion: The Smad4-independent pathway of TGF-?1 can increase the drug resistance of pancreatic cancer cells through upregulating expression of p170.