上海交通大学学报（医学版）

上海交通大学学报（医学版）

• 论著（基础研究） • 上一篇    下一篇

缺氧诱导因子-1α对低氧诱导自噬的调控作用

唐中园1,2，张宁1，狄文1，李卫平1   

  1. 上海交通大学 医学院 1.附属仁济医院妇产科 上海市妇科肿瘤重点实验室， 上海 200127； 2.附属瑞金医院妇产科， 上海 200025
  • 出版日期:2015-12-28 发布日期:2016-01-21
  • 通讯作者: 李卫平, 电子信箱: liweiping111@126.com。
  • 作者简介:唐中园 （1978—）， 女， 主治医师， 博士; 电子信箱: oignonet@gmail.com。
  • 基金资助:

    国家自然科学基金（81101972）； 2012年上海慈善慢跑基金。

Regulation of hypoxia-induced autophagy by hypoxia-inducible factor-1α

TANG Zhong-yuan1,2, ZHANG Ning1, DI Wen1, LI Wei-ping1   

  1. 1.Department of Obstetrics and Gynecology, Renji Hospital, Shanghai Key Laboratory of Gynecologic Oncology, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China; 2.Department of Obstetrics and Gynecology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
  • Online:2015-12-28 Published:2016-01-21
  • Supported by:

    National Natural Science Foundation of China, 81101972； Shanghai Charity Jogging Fund in 2012

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摘要：

目的  通过体外观察验证缺氧诱导因子-1α（HIF-1α）对自噬相关分子的调控作用。方法  采用Western blotting和免疫荧光技术，检测在常氧和缺氧培养体系下转染质粒或用药物干预人上皮性卵巢癌细胞株后HIF-1α和自噬相关分子的表达变化。结果  转染HIF-1α质粒后，在常氧状态下过度表达HIF-1α，Beclin 1亦见增加，LC3-Ⅰ转换成LC3-Ⅱ。在低氧状态下敲除HIF-1α后，Beclin 1表达可减少；原被低氧诱导的LC3-Ⅱ被抑制。喜树碱类药物NSC606985能抑制高转移卵巢癌细胞株的HIF-1α 自噬水平。结论  低氧微环境能够激活HIF-1α，并诱导上皮性卵巢细胞发生自噬。NSC606985在纳摩尔浓度即可发挥对HIF-1α的调控作用，但可因细胞类型不同而有差异，呈现正负不同的调控。

关键词: 缺氧诱导因子-1&alpha, ；自噬；缺氧

Abstract:

Objective  To verify the regulation of autophagy related molecules by hypoxia-inducible factor-1α (HIF-1α) through observation in vitro. Methods  Changes of expressions of HIF-1α and autophagy related molecules after human epithelial ovarian cancer cell lines being transfected by plasmids or intervened by drugs under normoxic or hypoxic culture condition were detected by Western blotting and immunofluorescence. Results  After being transfected by HIF-1α plasmids, HIF-1α was over-expressed, the expression of Beclin 1 increased, and LC3-Ⅰ converted to LC3-Ⅱ under the normoxic condition. After knockout of HIF-1α under the hypoxic condition, the expression of Beclin 1 decreased and LC3-Ⅱ induced by hypoxia was inhibited. Camptothecin drug NSC606985 inhibited the autophagy level of HIF-1α of high metastatic ovarian cancer cell lines. Conclusion  The hypoxic microenvironment can activate HIF-1α and induces the autophagy of epithelial ovarian cells. NSC606985 can regulate HIF-1α at nanomolar concentrations, but the effects on different cell types are different. The regulation may be positive or negative.

Key words: hypoxia-inducible factor-1α; , autophagy; , hypoxia