基础医学与临床 ›› 2008, Vol. 28 ›› Issue (5): 492-496.

• 研究论文 • 上一篇    下一篇

低氧通过HIF-1α上调卵巢癌细胞SKOV3中HPA的表达

袁彩霞 顾双 张淑红 张向宁   

  1. 山东大学齐鲁医院妇产科 山东大学齐鲁医院妇产科 解放军第456医院 妇产科 山东大学齐鲁医院妇产科
  • 收稿日期:2007-08-27 修回日期:2007-12-11 出版日期:2008-05-25 发布日期:2008-05-25
  • 通讯作者: 张向宁

Hypoxia dependent HIF-1α to upregulate the expression of HPA in human ovarian cancer cell line SKOV3

Cai-xia YUAN, Shuang GU, Shu-hong ZHANG, Xiang-ning ZHANG   

  • Received:2007-08-27 Revised:2007-12-11 Online:2008-05-25 Published:2008-05-25
  • Contact: Xiang-ning ZHANG

摘要: 目的 探讨低氧条件下卵巢癌细胞株SKOV3中低氧诱导因子-1α(HIF-1α), 乙酰肝素酶(HPA)的表达变化及相互作用关系。方法 分组孵育细胞株,用免疫细胞化学定性检测HPA蛋白,western-blot和RT-PCR检测HIF-1α,HPA蛋白和mRNA。结果 HPA蛋白定位于胞质。低氧12h~36h HIF-1α蛋白表达明显高于对照组(P<0.05),而mRNA变化不明显。HIF-1α 抑制剂雷帕霉素可抑制蛋白表达水平。在低氧后各时间点HPA蛋白及mRNA表达均升高(P<0.05),雷帕霉素显著抑制 HPA蛋白及mRNA表达。结论 低氧可依赖HIF-1α 途径增强HPA的表达,进而促进肿瘤的浸润转移。

关键词: 卵巢癌, 乙酰肝素酶, 雷帕霉素, 低氧诱导因子-1α

Abstract: Objective To investigate the expression of hypoxia inducible factor- 1α ( HIF-1α) and heparanase ( HPA), and their relationship during hypoxia in human ovarian cancer cell line SKOV3 . Methods SKOV3 cells were incubated in different groups ,immucytochemistry was applied to qualitatively assay HPA protein, western-blot was used to detect the protein expression of HIF-1α and HPA, and mRNA expression was determined by RT-PCR. Results The positive expression of HPA localized in cytoplasma. Western-blot analysis revealed that the protein expression of HIF-1α was significantly increased (P<0.05) under hypoxia for 12h, and remained at high level for 24h and 36h(P<0.05) . Compared with the unchanged mRNA expression of HIF-1α , rapamycin couldn't chang the tendency, however, it inhibited the up-regulation of HIF-1α protein expression. Meanwhile the protein and mRNA expression of HPA remained the increasing tendency markly (P<0.05) during 12-36h period. And HPA expression was also decreased abundantly after utilizing rapamycin . Conclusions Hypoxia promotes the expression of HPA through the HIF-1α pathway ,which plays an important role in the metastasis of ovarian cancer.

Key words: ovarian neoplasms, heparanase, rapamycin, hypoxia inducible factor-1α