趋化因子受体-4和乏氧诱导因子-1α双抑制对MCF-7细胞的影响

Effect of CXCR4 and HIF-1α dual inhibition with siRNA on MCF-7 breast cancer cells

目的同时抑制乳腺癌细胞株表达的趋化因子受体-4(CXCR4)和乏氧诱导因子-1α(HIF-1α),并考察其对乳腺癌细胞株MCF-7的影响。方法应用RNA干扰策略,通过优化siRNA序列和改造U6启动子,构建能够在乳腺癌缺氧微环境特异性表达的增强型启动子5HRE-U6(△U6p),并能同步沉默CXCR4和HIF-1α双基因的siRNA重组腺病毒表达系统,再通过体外侵袭试验考察抑制作用的有效性。结果 Ad-HIF-1/αCXCR4-siRNA能够抑制MCF-7的侵袭,较单一抑制CXCR4效果更强。结论趋化因子受体-4和乏氧诱导因子-1α的双靶向抑制较单独抑制前者更有效,可能成为抑制其转移的新靶标。

Objective To observe the influence of both CXCR4 and HIF-1α inhibited with siRNA on MCF-7 breast cancer cells.Methods RNA interference strategy was used by optimizing siRNA sequence and U6 promoter for the purpose of that could be expressed solely in cancer hypoxic microenvironment nitch,and an adenovirus recombinant siRNA system was constructed with a 5HRE-U6（△U6p）enhanced promoter that can simultaneously silence both CXCR4 and HIF-1α genes.siRNA inhibition to tumor cell invasion was tested in vitro.Results Ad-HIF-1α/CXCR4-siRNA inhibited MCF-7 cell invasion and was more effective than CXCR4 alone.Conclusion These results suggest that targeting both CXCR4 and HIF-1α is more effective than CXCR4 alone,and the two molecules may be a novel target for breast caner therapy.