缺氧诱导因子-1α过表达可使卵巢癌细胞株SKOV3的E-钙黏蛋白下调  

Over expression of HIF-1α decreased E-cad expression in human ovarian cancer cell line SKOV3

作　　者：高蜀君[1] 丰有吉[1] 孙红[1] 殷莲华[2] 

机构地区：[1]复旦大学附属妇产科医院妇科,上海200011 [2]复旦大学上海医学院生理和病理生理学系,上海200032

出　　处：《复旦学报（医学版）》2006年第4期441-444,共4页Fudan University Journal of Medical Sciences

基　　金：国家自然科学基金(30471806);上海市医学重点学科建设项目--妇产科学(05-Ⅲ0169)资助

摘　　要：目的探讨缺氧诱导因子-1α(Hypoxia-inducible factor1α,HIF-1α)和E-钙黏蛋白(E-cadherin,E-cad)在人卵巢浆液性肿瘤细胞SKOV3缺氧不同时间的表达及其相互作用关系。方法在细胞缺氧培养不同时间段,分别采用Western blotting和RT-PCR技术检测HIF-1α和E-cad的蛋白和RNA表达变化;同时用HIF-1α抑制剂雷帕霉素作用于细胞,检测上述各指标的变化。结果随着缺氧时间的延长,HIF-1α蛋白表达逐渐上升,缺氧16h达到高峰,24h仍处于较高水平(P<0.05),而HIF-1α的mRNA表达变化无明显改变(P>0.05);E-cad缺氧8h表达明显下降(P<0.05),缺氧24h表达仅为对照组的6.37%(P<0.05);雷帕霉素可以从蛋白水平抑制HIF-1α表达,防止E-cad在缺氧环境中的降低。结论HIF-1α过表达可通过下调E-cad从而降低SKOV3细胞的黏附能力,由此可能启动肿瘤细胞从原发灶脱落继而转移的第一步。Purpose To investigate the relationship between HIF-1α and E-cadherin（E-cad） expressions during hypoxia in human ovarian cancer cell line SKOV3. Methods Total amounts of HIF-1α and E-cad protein in SKOV3 cell, which were hypoxia with or without rapamycin, was examined by Western blot;RT-PCR was used to detect the difference in mRNA level. Results HIF-1α expression of SKOV3 increased when cells were exposed to hypoxia and reached peak at hypoxia 16 hours（P〈 0.05）. The subsequent expression of E-cad reduced significantly after hypoxia （P〈0.05） and kept declining with the time of hypoxia prolonged. Rapamycin could inhibit the up-regulation of HIF-1α protein in hypoxia and maintain E-cad expression at a relative high level. Conclusions HIF-1α might be an up-stream regulator of E-cad and it＇s over expression may play an important role in ovarian cancer peritoneal dissemination and plantation, metastasis of ovarian cancer.

关 键 词：卵巢癌细胞SKOV3 缺氧 缺氧诱导因子-1Α E-钙黏蛋白 

分 类 号：R373.31[医药卫生—病原生物学] R730.23[医药卫生—基础医学]