三种逆转剂对人膀胱癌多药耐受相关蛋白介导的多药耐受逆转的研究

目的：观察环孢霉素Ａ（ＣｓＡ）、维拉帕米（Ｖｅｒ）、黄体酮（Ｐｒｏｇ）对膀胱癌多药耐受相关蛋白（ＭＲＰ）介导的多药面受（ＭＤＲ）的塑转作用。方法：分别采用ＭＴＴ方法和流式细胞仪检测观察ＣｓＡ、Ｖｅｒ和Ｐｒｏｇ塑转化疗药物ＶＣＲ对ＭＲＰ高表达的膀胱癌细胞的细胞毒性作用的塑转效果。以及地细胞内柔红霉素（ＤＮＲ）聚集、外排的影响。结果：ＣｓＡ和Ｖｅｒ作为多药耐受糖蛋白（Ｐｇｐ）的良好剂同样可以显著逆转ＶＣＲ对Ｍ％ＲＰ高表达的ＥＪ／ＭＲＰ细胞毒性作用，具有增加ＥＪ／ＭＲＰ细胞内ＤＮＲ的聚集百的作用。剂量越大作用越强；而Ｐｒｏｇ则无类似作用。结论：ＣｓＡ和Ｖｅｒ对人膀胱癌ＭＲＰ介导的ＭＤＲ具有良好的逆转作用。可通过增加细胞内的药物聚集和减少外排已进入细胞内的药物起作用。这种作用存在剂量依从关系。

The reversal effect of CsA, verapamil and progesterone on MRP-mediated MDR in human bladder carcinoma cells

Purpose:To investigate the reversal effects of Cyclosporine (CsA),Verapamil (Ver) and Progesterone (Prog) on multidrug resistant associated protein (MRP) mediated MDR in bladder carcinoma.Methods:The reversal effects of three modulators on cytotoxicity of VCR to MRP overexpressed bladder carcinoma cells and the influence on intracellular drug accumulation and efflux were observed by using drug sensitivity testing (MTT method) and flow cytometry detection respectively.Results:CsA and Ver, which are good modulators of P-gp, could significantly improve the sensitivity of MRP overexpressed bladder to VCR, and increase intracellular DNRaccumulation and decrease intracellular DNR efflux. The higher the dose, the more significant the effects. Prog has no similar effects.Conclusions:Our studies revealed that CsA and Ver had significant reversal effects on MRP mediated MDR in human bladder carcinoma probably by decreasing drug accumulation and increasing intracellular drug efflux, and these effects were dose dependent.