凋亡抑制基因在人卵巢癌细胞敏感株及耐药株中的表达  

Differential Expression of Bcl-2 and Bcl-XL Genes in Cisplatin-sensitive and Resistant Human Ovarian Cancer Cell Lines

作　　者：于利利[1] 王泽华[1] 

机构地区：[1]华中科技大学同济医学院附属协和医院妇产科,武汉430022

出　　处：《华中科技大学学报（医学版）》2007年第5期637-639,共3页Acta Medicinae Universitatis Scientiae et Technologiae Huazhong

基　　金：国家自然科学基金资助项目(No30070786)

摘　　要：目的探讨凋亡抑制基因Bcl-2和Bcl-XL在人卵巢癌细胞敏感株(A2780)及耐药株(AD6)中的表达及其在卵巢癌多药耐药发生中的分子机制。方法采用DNA电泳、流式细胞技术及半定量逆转录多聚酶链式反应(RT-PCR)技术,检测不同浓度(3.0、6.0、9.9μg/ml)顺铂诱导的人卵巢癌细胞敏感株A2780及耐药株AD6的细胞凋亡及其Bcl-2和Bcl-XL基因的表达水平。结果①DNA凝胶电泳显示,不同浓度的顺铂均能诱导A2780和AD6细胞产生凋亡,呈现典型的凋亡梯度(DNA Ladder)。②流式细胞仪分析结果显示,不同顺铂浓度作用下A2780和AD6细胞凋亡率不同,AD6明显低于A2780(P<0.05)。③RT-PCR结果显示,A2780和AD6细胞均表达Bcl-2、Bcl-XL,但在AD6细胞株中2基因的表达明显强于A2780。在6.0μg/ml顺铂作用下A2780和AD6细胞株中2基因表达下调,但仍以在AD6的表达强于A2780。结论顺铂可诱导卵巢癌细胞凋亡,凋亡抑制基因Bcl-2和Bcl-XL在人卵巢癌多药耐药细胞株中高表达,是导致其细胞凋亡受抑制和对药物敏感性降低的重要原因。Objective To investigate the expression of Bcl-2 and Bcl-XL gene in sensitive（A2780） and drug-resistance（AD6） human ovarian cancer cell lines and explore the molecule mechanism of multidrug resistance.Methods The expression of Bcl-2 and Bcl-XL genes was detected by using semi-quantitative reverse transcription polymerase chain reaction（RT-PCR） following the exposure of A2780 and AD6 cells to cisplatin（6.0 μg/ml）.Apoptosis of A2780 and AD6 cells induced with different doses of cisplatin was assayed by DNA agarose gel electrophoresis and flow cytometry.Results DNA gel electrophoresis revealed that different doses of cisplatin could induce apoptosis of A2780 and AD6 cells and the intensity of DNA ＂Ladder＂ was enhanced in a dose-dependent manner.Flow cytometry showed the apoptosis rate of A2780 treated with difference doses of cisplatin was significantly higher than that of AD6（P〈0.05）.The expression levels of Bcl-2 and Bcl-XL genes in AD6 were higher than those in A2780.After treatment with cisplatin,the expression of Bcl-2 and Bcl-XL genes was down-regulated in A2780 and AD6 cells.Conclusion Cisplatin could induce the apoptosis of ovarian cancer cells,and the over-expression of Bcl-2 and Bcl-XL genes may contribute to apoptosis inhibition and the development of multidrug resistance of human ovarian cancer.

关 键 词：卵巢癌 细胞凋亡 多药耐药 基因BCL-2 基因Bcl-XL 顺铂 

分 类 号：R737.31[医药卫生—肿瘤]