TGF-β1的非Smad4依赖性途径与胰腺癌细胞耐药性的相关性

Relationship between Smad4-independent pathway of TGF-β1 and drug-resistance of pancreatic cancer cell line

目的:研究TGFβ1的非Smad4依赖性途径与胰腺癌耐药性之间的相关性。方法:采用MTT法观察Smad4纯合性缺失的胰腺癌细胞株BxPC3对不同化疗药物(5Fu、健择、草酸铂、顺铂、开普拓和表柔比星)的敏感性差异;MTT法观察转染了pcDNA3TGFβ1质粒的BxPC3细胞及5ng/ml和10ng/mlTGFβ1作用后的BxPC3细胞对顺铂敏感性的影响、蛋白免疫印迹检测TGFβ1作用后p170的改变情况。结果:BxPC3细胞对健择和表柔比星的敏感性最差,5Fu、开普拓和草酸铂次之,顺铂作用最强。转染了TGFβ1全长cDNA质粒的BxPC3细胞对顺铂的耐受能力增强;给予TGFβ1细胞外刺激后,也能增加细胞对顺铂的耐受能力。蛋白免疫印迹表明TGFβ1能增加p170(mdr1)的表达。结论:TGFβ1的非Smad4依赖性途径能通过上调p170的表达而增加肿瘤细胞的耐药性。

Objective.. To investigate ,he relationship between the Smad4-independent pathway of TGF-β1 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 eDNA of TGF-β1 or treated with TGF-β1 （5 and 10 ng/ml） solution. Western blot was used to detect p170 protein expression after stimulation with different concentrations of TGF-β1. 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 eDNA of TGF-β1 or treated with TGF-β1 solution became less sensitive to Cisplatin. Western blot revealed upregulation of p170 expression by TGF-β1. Conclusion： The Smad4-independent pathway of TGF-β1 can increase the drug resistance of pancreatic cancer cells through upregulating expression of p170.