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中国癌症防治杂志

中国癌症防治杂志

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RNAi抑制HIF-1α基因逆转卵巢癌多药耐药的实验研究

葛红雨;吴维光;韩建秋;王勇梅;   

  1. 华北煤炭医学院;武警医学院附属医院妇产科;
  • 收稿日期:2010-03-25 修回日期:2010-03-25 出版日期:2010-03-25 发布日期:2010-03-25

Reversion of multidrug resistance by RNA interference targeting HIF-1α gene in ovarian cancer cells

GE Hong-yu,WU Wei-guang,HAN Jian-qiu,et al.   

  1. (North China Coal Medical College,Tangshan 063000.Department of Obstetrics and Gynecology,Affiliated Hospital of People's Armed Police Medical College,Tianjin 300162,China
  • Received:2010-03-25 Revised:2010-03-25 Online:2010-03-25 Published:2010-03-25

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被引次数

9

摘要： 目的探讨靶向缺氧诱导因子1α(hypoxia inducible factor-1α,HIF-1α)载体表达的小干扰RNA(small interferingRNA,siRNA)逆转卵巢癌细胞多药耐药的可行性。方法构建靶向HIF-1α短发夹状siRNA基因表达载体,脂质体介导转染人卵巢癌COC1/DDP细胞。Western blot法检测HIF-1α蛋白和P-糖蛋白(P-glycoprotein,P-gp)的表达;实时定量PCR(real time PCR)检测HIF-1α和多耐药基因1(mdr-1)mRNA的表达;MTT法检测COC1/DDP细胞对化疗药物顺铂的抗性。结果转染HIF-1α短发夹状siRNA真核表达载体的COC1/DDP细胞,低氧条件下HIF-1α蛋白及mRNA表达水平下降,同时mdr-1基因的mRNA及其编码的P-gp蛋白水平也明显下降,对顺铂的药物敏感性增加。结论HIF-1α短发夹状siRNA真核表达载体可有效地抑制卵巢癌COC1/DDP细胞HIF-1α和mdr-1基因的表达,逆转卵巢癌细胞的多药耐药。

关键词: 卵巢癌, 药物耐受性, 低氧诱导因子1α, RNA干忧

Abstract: Objective To explore the feasibility of reversing multidrug resistance by RNA interference targeted on hypoxia inducible factor 1α(HIF-1α) gene in ovarian cancer cells.Methods Small hairpin RNA eukaryotic expression vector targeted on HIF-1α gene was constructed and transfected into COC1/DDP cells with liposome.The mRNA and protein expressions of HIF-1α and MDR-1 were measured by real time PCR and Western blot.The multidrug resistant to anticancer agent Cisplatin was evaluated by MTT assay.Results After transfected with the small hairpin RNA eukaryotic expression vector targeted on HIF-1α gene,the mRNA and protein expressions of HIF-1α and MDR-1 in COC1/DDP cells decreased significantly under hypoxic condition.Furthermore,the sensitivity to Cisplatin significantly increased.Conclusions The small hairpin RNA eukaryotic expression vector targeted on HIF-1α gene can effectively suppress the expressions of HIF-1α and MDR-1 genes in ovarian cancer cells,and then can reverse the multidrug resistance.

Key words: Ovarian cancer, Drug tolerance, Hypoxia-inducible factor-1α, RNA interference