拓扑替康胞内浓度降低——卵巢癌细胞耐药的一种新机制  

Reduced Intracellular Concentration of Topotecan: A New Mechanism of Drug-resistance in Human Ovarian Cancer

作　　者：贾平[1] 吴少波[2] 李芳[1] 奚玲[1] 廖国宁[1] 卢运萍[1] 马丁[1] 

机构地区：[1]华中科技大学同济医学院附属同济医院妇产科,武汉430030 [2]武汉大学医学院生物化学教研室,武汉430071

出　　处：《华中科技大学学报（医学版）》2004年第6期737-741,共5页Acta Medicinae Universitatis Scientiae et Technologiae Huazhong

基　　金：国家杰出青年基金资助项目 (30 0 2 5 0 17) ;国家重点基础研究发展资助项目 (2 0 0 2CB5 1310 0 )

摘　　要：目的　探讨卵巢癌拓扑替康 (TPT)耐药细胞株中TPT胞内浓度的变化。方法　建立卵巢癌TPT耐药细胞株 ,四甲基偶氮唑蓝 (MTT)比色法检测该细胞株对多种化疗药物的耐药指数 ,流式细胞仪检测 2株细胞在不同条件下的TPT胞内浓度。结果　该细胞株对TPT及米托蒽醌 (MX)耐药。耐药细胞的TPT泵出速率明显快于亲本细胞的泵出速率 ,胞内TPT浓度约为亲本细胞的 1/ 6 (P <0 0 5 ) ;低温时 2株细胞的TPT泵出均受抑制 ;能量不足时 ,耐药细胞的TPT泵出减少 ,胞内浓度由 13 78增加到 2 0 13(P <0 0 5 )。结论　能量依赖性的拓扑替康胞内浓度降低是卵巢癌细胞耐药的一种机制。Objective To study the changes of intracellular concentration o f topotecan (TPT) in human ovarian cancer TPT-resistant cell line. Methods The ovarian cancer TPT-resistant cell line was establi shed and the resistant indexes of the resistant cell line to different chemother apeutic drugs were determined by the methyl thiazolyl tetrazolium assay. Intrace llular TPT concentration was measured by flow cytometry under different conditio ns. Results The drug-resistance to TPT and Mitoxantrone (MX) was i ndicated in resistant cells. The efflux rate of TPT was significantly increased in resistant cells as compared with parental cells whose intracellular concentra tion of TPT was approximately 6 folds of the resistant cells (P<0.05). The efflux of TPT from both cells was inhibited at lower temperature. Under energy-d eprived conditions, the efflux of TPT was decreased and the concentration of TPT was increased from 13.78 to 20.13 (P<0.05) in resistant cells. Conclusion The energy-dependently reduced intracellular conce ntration of topotecan appeared to be a novel mechanism of drug-resistance in hu man ovarian cancer.

关 键 词：TPT 耐药细胞株 拓扑替康 卵巢癌细胞 四甲基偶氮唑蓝 流式细胞仪检测 米托蒽醌 MTT 低温 依赖性 

分 类 号：R737.31[医药卫生—肿瘤] R734[医药卫生—临床医学]