异博定逆转肝癌细胞多药耐药的研究

Reversal Effects of Verapamil on Adriamycm Resistance of Human Liver Cancer Cells

肿瘤细胞对化疗药物产生多药耐药(MDR)是肿瘤化疗失败的主要原因,为了寻找克服肿瘤细胞多药耐药的方法,将异博定加入体外培养诱导的人肝癌细胞多药耐药株SMMC-7721/ADM中,MTT法检测显示异博定增加了化疗药对SMMC-7721/ADM细胞的毒性,并随异博定浓度的增加其逆转活性也增强,(VPL25μg/ml时,SMMC-7721/ADM的活细胞为65％,而VPL20μg/ml时,SMMC-7721/ADM的活细胞率为39％,两者有显著差异)。流式细胞技术显示异博定使耐药细胞表面P-糖蛋白的浓度降低和耐药细胞内柔红霉素的浓度增加(P-gp由70.13下降到22.68,DNR浓度由133上升到163),因此研究表明异博定逆转肿瘤细胞的多药耐药机理是通过使肿瘤细胞表面的P-糖蛋白表达减少,增加肿瘤细胞内的化疗药物浓度而起作用。

Resistance of tumor cells to many chemotherapeutic agents is a major obstacle in the treatment of several types of human cancer. To explore the reversal effects of verapamil on drug-resistance of hepatic cancer cells, verapamil was used as the reversal reagent for drug-resistance in hepatic cancer cells. The cytotoxicity of ADM and other anticancer drugs to SMMC-7721/ ADM was measured by MTT assay. It shows that the reversal effect was increased with the concentration of VPL (VPL 2. 5ug/ ml, SMMC-7721/ADM cells 65%, VPL 20ug/ml, SMMC-7721/ADM cells 39%, P<0. 01). Measurement of intracellular daunomycin (DNR) and membrane glycoprotein (P-gp) by was conducled flow cytometry; threatment of SMMC-7721/ADM cells with VPL increased the accumulation of intracellular DNR and decreased the efflux of drug and low expression of P-gp (P-gp from 70. 13 to 22. 68, DNR from 133 to 163). This research suggests that VPL may be useful in modulating MDR.