中文摘要：

目的探讨DNA拓扑异构酶（Topoisomerase,Topo）在卵巢癌拓扑替康（TPT）耐药细胞A2780/TPT中的作用。方法采用四甲基偶氮唑蓝（MTT）比色法检测该细胞株对TPT、米托蒽醌（MX）、喜树碱（CPT）、阿霉素（ADM）、鬼臼乙叉甙（VP-16）、顺铂（cDDP）的耐药指数。Western blot法检测TopoⅠ及TopoⅡ的蛋白含量,超螺旋DNA松解法检测TopoⅠ的酶活性。结果A2780/TPT细胞对TopoⅠ抑制剂TPT及CPT的耐药指数分别为25.1及3.1,对MX的耐药指数为19.0,对cDDP及TopoⅡ抑制剂ADM、VP-16仍保持敏感。耐药株的TopoⅠ含量约为亲本细胞的40%,且TopoⅠ活性下降（P〈0.05）,而TopoⅡ含量约为亲本细胞的2.2倍（P〈0.05）。结论TopoⅠ含量的下降及TopoⅡ含量的增加是卵巢癌TPT耐药细胞对TopoⅠ抑制剂及TopoⅡ抑制剂产生不同药敏情况的原因。

英文摘要：

Objective To study the roles of DNA topoisomerases（Topo） in ovarian cancer TPT-resistant cells, Methods The resistance index of A2780/TPT cells to different chemotherapeutic drugs was determined by the methyl thiazolyl tetrazolium assay. The expression of Topo Ⅰ and Topo Ⅱ was detected by Western blot, and the catalytic activity of Topo Ⅰ was determined by the relaxation of supercoiled PBR 322 DNA. Results The drug resistance index of A2780/TPT cells to Topo Ⅰ inhibitors TPT and CPT was 25.1 and 3.1 respectively, and to MX was 19.0. A2780/TPT cells still displayed sensitivity to cDDP and Topo Ⅱ inhibitors ADM and VP-16. The content of Topo Ⅰin the resistant cells was 40% of the parental cells and the catalytic activity of Topo Ⅰ decreased（P〈0.05）, but the content of Topo Ⅱ was 2.2 times of parental cells（P〈0.05）. Conclusion The different cytotoxicity to Topo Ⅰ inhibitors and Topo Ⅱ inhibitors in ovarian cancer TPT-resistant cells was due to the decreased Topo Ⅰ and increased Topo Ⅱ.