缺氧条件下雷帕霉素抗人乳腺癌MCF-7细胞增殖作用的研究  

The study of anti-proliferation effect of rapamycin on human breast cancer MCF-7 cells under hypoxia

作　　者：钱超[1] 夏锴[1] 张静静[1] 杜青[1] 刘晓安[1] 王水[1] 

机构地区：[1]南京医科大学第一附属医院普外科,江苏南京210029

出　　处：《南京医科大学学报（自然科学版）》2008年第6期742-746,770,共6页Journal of Nanjing Medical University(Natural Sciences)

基　　金：江苏省333高层次人才培养工程基金资助

摘　　要：目的:比较雷帕霉素、阿霉素单药或联合应用在常氧和缺氧条件下体外抗人乳腺癌MCF-7细胞的增殖能力。方法:采用MTT法和流式细胞仪检测在常氧或缺氧状态下雷帕霉素、阿霉素单独或联合使用时,对MCF-7细胞增殖和细胞周期的影响。Western blot检测不同氧浓度下及不同药物处理下MCF-7细胞HIF-1α、pAkt的表达。结果:与阿霉素相反,在缺氧条件下,雷帕霉素对MCF-7细胞的增殖抑制能力高于常氧条件。在2种氧浓度下,临床常用浓度(10ng/ml)的雷帕霉素和阿霉素联合使用无协同作用。雷帕霉素单独作用于MCF-7细胞主要表现为G1期阻滞,与阿霉素联用则表现为G2期细胞增多。缺氧使HIF-1α、pAkt表达增加。但10ng/ml的雷帕霉素对HIF-1α、pAkt表达无明显影响。结论:临床常用浓度范围内的雷帕霉素在缺氧状态下抗MCF-7细胞增殖能力增强,其原因可能是雷帕霉素对细胞的增值抑制作用不受HIF-1α表达的影响,缺氧使肿瘤细胞pAkt表达增加可能使其对雷帕霉素敏感性增加。Objective：This study was to determine the anti-proliferation effects of using rapamycin or adriamycin alone or combination of them on human breast cancer MCF-7 cells exposed to normal oxygen concentration or hypoxic enviroment in vitro. Methods：MTT assay and flow cytometry were used to examine the influence of the drugs on cell proliferation and cell cycle of MCF-7 cells. MCF-7 cells were exposed to normal or hypoxic enviroment and treated with rapamycin or adriamycin alone or co-treated with rapamycin and adriamycin. Western blot analysis was used to assess the expression level of HIF-1α and pAkt. Results：Opposite to adriamycin,the effect of rapamycin on inhibiting cell proliferation of MCF-7 cells was enhanced when exposed to hypoxia compared with the effect under normal oxygen environment. Regardless of oxygen concentrations,no synergistic interaction was observed when rapamycin at clinical normal drug level（10 ng/ml） combined with adriamycin on MCF-7 cells. The MCF-7 cells treated with rapamycin alone were arrested at G1,while co-treated with rapamycin and adriamycin were arrested at G2. Hypoxia enhanced the expression levels of HIF-1α and pAkt,while rapamycin at 10 ng/ml had no influence on the expression levels of HIF-1α and pAkt. Conclusions：Hypoxia increased the sensitivity of rapamycin on MCF-7 cells,which may be caused by increasing pAkt expression subsequent to hypoxia.

关 键 词：乳腺癌 缺氧 雷帕霉素 阿霉素 

分 类 号：R737.9[医药卫生—肿瘤]