错配修复基因hMLH1和hMSH2的表达与人卵巢癌顺铂耐药的关系  

Relationship of DNA Mismatch Repair Gene hMLH1 and hMSH2 Expression with Chemoresistance of the Cisplatin-Resistant Human Ovarian Cancer SKOV3/DDP Cell Line

作　　者：李渊渊[1] 何华 曾飚[1] 舒丹[1] 钟玲[1] 

机构地区：[1]重庆医科大学附属第二医院妇产科,重庆市400010 [2]福建省泉州市妇幼保健院妇科

出　　处：《中国肿瘤临床》2011年第15期875-877,881,共4页Chinese Journal of Clinical Oncology

摘　　要：目的:探讨DNA错配修复基因hMLH1和hMSH2的表达在人卵巢癌细胞顺铂耐药现象中的作用。方法:MTT法检测卵巢癌细胞对顺铂的敏感性,Hoechst免疫荧光染色检测顺铂作用下敏感及耐药细胞的凋亡情况,并使用RT-PCR技术及West-ern blotting技术分别检测顺铂敏感性人卵巢癌细胞及耐药顺铂人卵巢癌细胞中错配修复基因hMLH1及hMSH2的转录与翻译表达变化。结果:同一顺铂浓度作用下,耐药顺铂人卵巢癌细胞的凋亡率明显低于顺铂敏感性人卵巢癌细胞,且后者的错配修复基因hMLH1和hMSH2的mRNA及蛋白表达水平均显著高于前者。结论:顺铂可诱导卵巢癌细胞凋亡。在耐药顺铂人卵巢癌细胞中,错配修复基因hMLH1和hMSH2低表达可能是导致顺铂耐药发生的重要原因。Objective： To investigate the role of hMLH1 and hMSH2 gene expression in cisplatin resistance of human ovarian cancer （ OC ）. Methods： The chemosensitivity of OC to cisplatin was determined with an MTT assay. Hoechst fluorescence analysis was used to test the DDP-indueed sensitivity and apoptosis of the drug-fast cells, hMLH1 and hMLH2 expression at the transcriptional and translational levels in the DDP-sensitive SKOV3 cells and DDP-resistant SKOV3/DDP cell line were measured by reverse transcription polymerase chain reaction （ RT-PCR ） and Western blot analysis, respectively. Results： The apoptotic rate of the cell SKOV3/ DDP line was markedly lower than that of the SKOV3 cells after cisplatin administration at the same concentration. Both the mRNA and protein levels of hMLH 1 and hMSH2 were significantly higher in the SKOV3 than in SKOV3/DDP cells. Conclusion： Cisplatin induces the apoptosis of the SKOV3 and SKOV3/DDP cell lines. In the drug-tolerant SKOV3/DDP cells, the low expression of the hMLH1 and hMSH2 genes may be the major cause of the occurrence of cisplatin resistance.

关 键 词：卵巢癌 顺铂 耐药 

分 类 号：R737.31[医药卫生—肿瘤]