Bullatacin克服肿瘤多药抗药性作用及其机理  

THE CIRCUMVENTION OF TUMOR MULTIDRUG RESISTANCE BY BULLATACIN AND ITS MECHANISM

作　　者：符立梧[1,2] 谭炳炎[1,2] 梁永钜[1,2] 潘启超[1,2] 黄红兵 冯公侃[1,2] 

机构地区：[1]中山医科大学肿瘤防治中心 [2]中山医科大学分子医学中心

出　　处：《药学学报》1999年第4期268-271,共4页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金

摘　　要：目的：探讨ｂｕｌａｔａｃｉｎ克服肿瘤多药抗药性（ＭＤＲ）的作用及其机制。方法：以两对ＭＤＲ细胞株及其相应的敏感株进行对比，比较两种细胞株的细胞毒、Ｆｕｒａ２及阿霉素细胞内积累。结果：ｂｕｌａｔａｃｉｎ不仅对敏感细胞株具有很强的细胞毒活性，而且对ＭＤＲ细胞株也同样具有很强的细胞毒活性，不受抗药性的影响。ｂｕｌａｔａｃｉｎ能使ＭＤＲ细胞内Ｆｕｒａ２的积累增加；也能增加ＭＤＲ细胞内阿霉素的积累。结论：ｂｕｌａｔａｃｉｎ具有克服ＭＤＲ的作用，其作用机理与ｂｕｌａｔａｃｉｎ影响ＭＤＲ细胞Ｐｇｐ的功能。AIM: To find new drugs to overcome tumor multidrug resitance(MDR), bullatacin was studied with technique of cell culture in vitro. METHODS: The study was carried out using two pairs of cell lines: MDR cell lines and their parental sensitive cell lines including MCF7/Adr cells and MCF7 cells, KBv200 cells and KB cells. Cytotoxicity was determined with tetrazolium (MTT) assay. The function of Pgp was examined by Fura2/AM assay. Cellular accumulation of adriamycin(ADM) was determined by fluorescence spectrophotometry measurement (to reflect cellular bullatacin accumulation). RESULTS: Bullatacin showed potent cytotoxicity to MCF7/Adr cells, MCF7 cells, KBv200 cells and KB cells. The cytotoxicities of bullatacin to MDR cells were similar to that to parental sensitive cells. Bullatacin markedly increased cellular Fura2 and ADM accumulation in MCF7/Adr cells, while not in MCF7 cells. CONCLUSION: There was no crossresistance of bullatacin to Pglycoproteinpositive MCF7/ADR and KBv200 cell lines as co mpared with their sensitive cell lines. The mechanism of overcoming MDR was associated with the decrease of Pgp function and the increase of MDR cellular drug accumulation.

关 键 词：Bullatacin 多药抗药性 P-糖蛋白 番荔枝内酯 

分 类 号：R979.1[医药卫生—药品] R730.5[医药卫生—药学]