低氧通过HIF-1α上调卵巢癌细胞系SKOV3中HPA的表达  

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

作　　者：袁彩霞[1] 顾双[1] 张淑红[2] 张向宁[1] 

机构地区：[1]山东大学齐鲁医院妇产科,山东济南250012 [2]解放军第456医院妇产科,山东济南250031

出　　处：《基础医学与临床》2008年第5期492-496,共5页Basic and Clinical Medicine

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12—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。Objective To investigate the expression of hypoxia inducible factor-1α （HIF-1α） and heparanase （HPA）, and their re1αtionship 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 cytop1αsma. Western-blot analysis revealed that the protein expression of HIF-1α was siguificantly increased （P 〈0. 05） under hypoxia for 12 h, and remained at high level for 24 h and 36 h （P 〈 O. 05 ）. Compared with the unchanged mRNA expression of HIF-1α, rapamycin couldn＇ t chang the tendency, however, it inhibited the up-regu1αtion of HIF-1α protein expression. Meanwhile the protein and mRNA expression of HPA remained the increasing tendency markedly （ P 〈 O. 05 ） during 12 ~ 36 h period. And HPA expression was also decreased abundantly after utilizing rapamycin. Conclusion Hypoxia promotes the expression of HPA through the HIF-1α pathway, which p1αys an important role in the metastasis of ovarian cancer.

关 键 词：卵巢癌 低氧诱导因子-1Α 乙酰肝素酶 雷帕霉素 

分 类 号：R737.31[医药卫生—肿瘤]