缺氧条件下缺氧诱导因子-1α抑制剂YC-1对人卵巢癌Skov3干细胞耐药的逆转作用

Under hypoxic conditions hypoxia-inducible factor-la inhibitor YC-1 human ovarian cancer stem cells Skov3 resistance reversal effect

目的:探讨缺氧诱导因子-1α抑制剂YC-1在缺氧条件下逆转人卵巢癌干细胞Skov3耐药的机制。方法:选用人卵巢癌Skov3细胞通过无血清悬浮培养法富集肿瘤干细胞。分别于常氧及缺氧条件下检测不同浓度顺铂干预Skov3贴壁细胞及干细胞后测定顺铂对于两种细胞的抑制作用,及缺氧后干性指标、耐药指标ABCG2及HIF-1α的表达。当给予HIF-1α抑制剂YC-1后,测定顺铂对Skov3干细胞的抑制作用。并且检测干细胞干性指标、ABCG2及HIF-1α的mRNA表达。结果:悬浮培养的Skov3干细胞的干性指标CD44、NANOG、OCT-4及耐药指标ABCG2较贴壁细胞升高,且缺氧培养后,随着HIF-1α表达的升高,CD44、NANOG、OCT-4及ABCG2的表达也明显升高,P<0.05。干细胞的耐药性高于贴壁细胞,且缺氧培养耐药性增加。当给予YC-1后,干细胞耐药性下调,HIF-1α出现抑制,同时其干性指标CD44、NANOG、OCT-4、耐药ABCG2明显下调,P<0.05。结论:YC-1在缺氧条件下通过抑制HIF-1α下调ABCG2的表达逆转Skov3干细胞耐药。

Objective：To study the mechanism of hypoxia inducible factor 1α inhibitor YC-1 reversal of drug resistance in ovarian cancer stem cells Skov3 inhibitor under hypoxic conditions.Methods：Skov3 human ovarian cancer cells in serum-free suspension culture enriched cancer stem cells.Being measured after different concentrations of cisplatin intervention Skov3 adherent cells and stem cells under normoxic and hypoxic conditions cisplatin for both cells in vitro,and hypoxia dry index,resistance index of ABCG2 and HIF-1α expression.When administered HIF-1α inhibitor YC-1 was measured after cisplatin for Skov3 stem cells.And to detect stem cells dry,ABCG2 and HIF-1α mRNA of tables.Results：Stem index CD44 suspension culture Skov3 stem cells,NANOG,OCT-4,and ABCG2 resistance index increased compared with adherent cells,and hypoxia,along with the increased expression of HIF-1α,CD44,NANOG,OCT-4,and the expression of ABCG2 expression was significantly increased,P〈0.05.Stem cells resistance above adherent cells,and hypoxia increased drug resistance.YC-1 when administered after stem cell drug resistance down,HIF-1α inhibition occurs,while its dry index CD44,NANOG,OCT-4,drug significantly reduced ABCG2,P〈0.05.Conclusion：YC-1 expression under hypoxic conditions down reverse Skov3 ABCG2 stem cell drug by inhibiting HIF-1α.