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  

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

作　　者：章小平[1] 杨红枚 鲁功成[1] 

机构地区：[1]同济医科大学附属协和医院泌尿外科,武汉430022 [2]同济医科大学附属协和医院检验科

出　　处：《临床泌尿外科杂志》2000年第12期559-561,共3页Journal of Clinical Urology

基　　金：国家自然科学基金!资助项目 (编号 396 70 72 3)

摘　　要：目的 :观察环孢霉素 A(Cs A)、维拉帕米 (Ver)、黄体酮 (Prog)对膀胱癌多药耐受相关蛋白 (MRP)介导的多药耐受 (MDR)的逆转作用。方法 :分别采用 MTT方法和流式细胞仪检测观察 Cs A、Ver和 Prog逆转化疗药物 VCR对 MRP高表达的膀胱癌细胞的细胞毒性作用的逆转效果 ,以及对细胞内柔红霉素 (DNR)聚集、外排的影响。结果 :Cs A和 Ver作为多药耐受糖蛋白 (P- gp)的良好剂同样可以显著逆转 VCR对 MRP高表达的 EJ/MRP细胞毒性作用 ,具有增加 EJ/ MRP细胞内 DNR的聚集和减少外排的作用 ,剂量越大作用越强 ;而 Prog则无类似作用。结论 :Cs A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。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.

关 键 词：抗肿瘤药 多药耐受相关蛋白 膀胱肿瘤 耐药性 

分 类 号：R737.140.5[医药卫生—肿瘤] R979.1[医药卫生—临床医学]