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作 者:袁晶[1] 郭秋艳[1] 韩晗[1] 吴春凤[1] 黄明莉[1] 张广美[1]
机构地区:[1]哈尔滨医科大学附属第一医院妇产科,黑龙江哈尔滨150001
出 处:《哈尔滨医科大学学报》2014年第6期472-475,共4页Journal of Harbin Medical University
基 金:黑龙江省教育厅科学技术研究项目(12541555)
摘 要:目的探讨卵巢癌细胞中,HIF-1α与GST-π表达的相关性及NF-κB的调节作用,为卵巢癌耐药的基因治疗提供重要靶点。方法卵巢癌SKOV3细胞转染HIF-1αsiRNA,检测其转染效率;采用RT-PCR和Western blot法检测HIF-1α基因沉默后卵巢癌细胞中GST-π以及NF-κB基因和蛋白表达的变化;给予不同浓度NF-κB抑制剂PDTC后,检测GST-π和NF-κB的表达变化。结果 HIF-1α的siRNA载体成功转染卵巢癌SKOV3细胞后,HIF-1αmRNA表达显著下降,GST-π的mRNA和蛋白表达抑制,NF-κB表达增加。给予NF-κB抑制剂PDTC后,随着抑制剂浓度增加,GST-π表达增加。结论靶向沉默HIF-1α降低卵巢癌耐药因子GST-π的表达,增加卵巢癌细胞对化疗的敏感性。NF-κB可能参与HIF-1α沉默后引起GST-π表达下降的调节途径。Objective To investigate the expression of HIF-1α, GST-πand NF-κB in epitheli-al ovarian tumors , in order to provide a target for the gene therapy for drug resistance in epithe-lial ovarian cancer .Methods Following the transfection of HIF-1αsiRNA in ovarian cancer SKOV3 cells, the efficiency of transfection was detected .The gene and protein expression lev-els of GST-πand NF-κB were determined by RT-PCR and Western blot after HIF-1αsilencing in SKOV3 cells.The changes in GST-πand NF-κB expression were tested after different con-centrations of PDTC , a NF-κB pathway inhibitor , were applied .Results After SKOV3 cells were transfected with P Super HIF-1αsiRNA, there was a significant decrease in the expression of HIF-1αmRNA;in addition , the mRNA and protein levels of GST-πwere suppressed , while those of NF-κB were increased .After PDTC was added , GST-πexpression was elevated with the increase of inhibitor concentrations .Conclusion Targeted silence of HIF-1αin epithelial ovarian cancer cells can reduce the expression of drug resistance factor GST-πand enhance the chemotherapeutic sensitivity .NF-κB may take part in the regulation of GST-πexpression in the case of HIF-1αsilencing .
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