Objective To investigate the reversal effect and mechanism of emodin on gemcitabine resistant of pancreatic cancer cell line(Bxpc-3/Gem).Methods A gemcitabine-resistant cell line Bxpc-3/Gem was derived from the human pancreatic cancer cell line Bxpc-3.The pancreatic cancer cell lines Bxpc-3/Gem and Bxpc-3 were treated with various concentrations of emodin,gemcitabine and the combination of emodin + gemcitabine, Bxpc-3/Gem cells were treated with emodin(40μm)and gemcitabine(20μm)alone or together for 48 h,and then the changes in gene expression were detected by RT-PCR,DNA-binding activity of NF-κB by EMSA.Results Emodin reduced Bxpc-3/Gem cell proliferation and caused apoptosis in a dose-dependent manner. Emodin and gemcitabine combination treatments resulted in decreased cell proliferation. In addition,combination treatments resulted in downregulation of gene expression of NF-κB,as well as inhibition of NF-κB function.Conclusion These observations suggest that emodin can sensitize the pancreatic cancer gemcitabine-resistant cell line Bxpc-3/Gem to gemcitabine therapy via NF-κB.%目的 探讨大黄素逆转胰腺癌耐药细胞株Bxpc-3/Gem耐药作用及其逆转机制.方法 采用浓度递增法诱导建立耐药细胞株Bxpc-3/Gem;胰腺癌细胞株Bxpc-3/Gem和Bxpc-3经不同浓度大黄素作用48h,MTT法检测细胞增殖;以及大黄素(40μm)及吉西他滨(20μm)处理细胞48h,应用MTT法检测Bxpc-3/Gem和Bxpc-3细胞增殖;RT-PCR检测经大黄素及吉西他滨处理后的Bxpc-3/Gem细胞中NF-κB基因的表达水平;凝胶电泳迁移率实验(EMSA)检测经大黄素及吉西他滨处理后Bxpc-3/Gem细胞中NF-κB的活性.结果 大黄素对Bxpc-3/Gem细胞的增殖抑制作用呈明显的浓度依赖性;大黄素显著增强吉西他滨对Bxpc-3/Gem细胞的增殖抑制作用;大黄素单独及联合吉西他滨均可下调细胞中NF-κB基因的表达,抑制NF-κB的活性.结论 大黄素可以逆转胰腺癌耐药细胞株Bxpc-3/Gem的耐药作用,其机制可能是下调NF-κB的表达,抑制其活性从而增强胰腺癌细胞对吉西他滨的敏感性.
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