DNA拓扑异构酶在卵巢癌细胞拓扑替康耐药中的作用  

Roles of DNA Topoisomerases in Ovarian Cancer Topotecan-resistant Cells

作　　者：贾平 卢运萍[2] 马丁[2] 

机构地区：[1]湖北省襄樊市第一人民医院妇产科,襄樊441000 [2]华中科技大学同济医学院附属同济医院妇产科,武汉430030

出　　处：《华中科技大学学报（医学版）》2008年第1期69-72,共4页Acta Medicinae Universitatis Scientiae et Technologiae Huazhong

基　　金：国家杰出青年基金资助项目(No30025017)

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。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.

关 键 词：拓扑异构酶 拓扑异构酶Ⅰ抑制剂 拓扑异构酶Ⅱ抑制剂 卵巢癌 拓扑替康耐药 

分 类 号：R737.31[医药卫生—肿瘤]