苄丙洛逆转肿瘤多药抗药性作用及其机理的探讨  

Reversal of multidrug resistance and its mechanism by bepridil

作　　者：符立梧[1,2] 潘启超[1,2] 张永明[1,2] 杨小平[1,2] 

机构地区：[1]中山医科大学肿瘤研究所药物室 [2]中山医科大学附属三院药剂科

出　　处：《癌症》1998年第3期178-181,共4页Chinese Journal of Cancer

基　　金：博士点基金

摘　　要：目的：为了探讨新的钙阻断剂苄丙洛逆转肿瘤多药抗药性（ＭＤＲ）的作用及其机理。方法：以Ｆｕｒａ－２／ＡＭ法测定Ｐ－糖蛋白功能，ＭＴＴ法测定细胞毒作用，细胞内阿霉素（Ｄｏｘ，ＡＤＲ）测定以荧光分光光度计法，细胞内钙离子测定用Ｆｕｒａ－２－ＡＭ法。结果：苄丙洛能显著增加ＤＮＲ细胞内Ｆｕｒａ－２的积累和降低ＭＣＦ－７／ＡＤＲ细胞对ＡＤＲ的ＩＣ５０，对相应的敏感细胞株ＭＣＦ－７无此作用。在相同的浓度下（１０μｍｏｌ／Ｌ），其逆转活性较维拉帕米强。苄丙洛能显著地增加ＭＤＲ细胞内Ｄｏｘ的积累。高钙或低钙离子浓度不能改变ＭＤＲ细胞内Ｄｏｘ积累，苄丙洛也不能改变ＭＤＲ细胞内游离钙离子浓度。结论：苄丙洛能在体外逆转ＭＤＲ，且较维拉帕米强。其逆转机理与增加细胞内抗癌药物的积累有关，与钙离子浓度无关。Aim: To explore the reversal of multidrug resistance (MDR) and its mechanisms by bepridil which is a new calcium channel blocker. Methods: The cellular accumulation of Fura-2 and fold-reversal were studied with Fura-2/AM and MTT assay, respectively. Cellular doxorubicin (Dox) accumulation was measured by fluorescence spectrophotometry. Cellular free calcium ion concentration was determined with Fura 2-AM. Results: Bepridil significantly increased the celluar accumulation of Fura-2 in MCF-7/ADR cells and increased cytotoxicity in MCF-7/ADR cells to adriamycin and KBv200 cells to vincristine, but not increase in the actions on their parental sensitive cells. Bepridil had more potent reversal action on MDR cells than verapamil under equimolar concentration (10 μmol/L). The cellular Dox accumulation was markedly increased in the presence of bepridil in MDR cells. No effect was observed for ADR accumulation in the high or concentration. And cellular free calcium ion was not changed by bepridil in MDR cells. Conclusions: Bepridil was potental MDR reverser in vitro. Its reversal mechanism was associated with the increase of the cellular accumulation of anticancer drug and without relation to calcium ion concentration.

关 键 词：苄丙洛 药理学 多药抗药性 肿瘤 

分 类 号：R972[医药卫生—药品] R730.53[医药卫生—药学]