芒柄花素抑制乳腺癌细胞 HIF －1α／CXCR4信号以及细胞增殖和迁移

摘要

目的：研究芒柄花素对乳腺癌细胞行为的影响及其作用机制。方法利用不同浓度（5、10、15、20μM）的芒柄花素处理 MDA －MB －231细胞，分别处理48 h。应用 qRT －PCR 法检测细胞中低氧诱导因子－1α（HIF －1α）和 CXC 趋化因子受体4（CXCR4）mRNA 的表达，利用 Western blot 方法检测细胞中 HIF －1α和 CXCR4蛋白的表达。构建pShuttle －HIF －1α过表达载体并转染 MDA －MB －231细胞。利用噻唑蓝（MTT）法检测细胞增殖，利用 Transwell 法检测细胞体外迁移。结果相比于对照组，芒柄花素显著降低 MDA －MB －231细胞中 HIF －1α和 CXCR4 mRNA 和蛋白的表达水平（P ＜0.05），并且具有剂量依赖性。过表达 HIF －1α提高芒柄花素处理后细胞中 HIF －1α和 CXCR4的表达水平（P ＜0.05），促进癌细胞增殖（P ＜0.05），并促进癌细胞体外迁移（P ＜0.05）。结论芒柄花素可能通过调控乳腺癌细胞中 HIF －1α／CXCR4信号转导影响癌细胞增殖和迁移。%Objective To investigate the effect of formononetin on breast cancer cell behavior as well as its mechanism. Methods MDA -MB -231 cells were exposed to different doses (5,1 0,1 5,20 μM)of formononetin for 48 h respectively. The expression of hypoxia -inducible factor -1 α(HIF -1 α)mRNA and CXC chemokine receptor 4 (CXCR4)mRNA were an-alyzed by qRT -PCR.The expression of HIF -1 αand CXCR4 protein were analyzed by Western blot method.Furthermore, pShuttle -HIF -1 αoverexpression vector was constructed and transfected into MDA -MB -231 cells.Cell proliferation was de-termined by MTT assay.Cell migration was evaluated by Transwell assay.Results Compared with the control,exposure of for-mononetin significantly decreased both mRNA and protein expression of HIF -1 αand CXCR4 (P <0.05)in a dose dependent way.Overexpression of HIF -1 αraised HIF -1 αand CXCR4 expression in cancer cells after formononetin treatment (P <0.05),promoting cell proliferation (P <0.05)and enhancing cell migration (P <0.05).Conclusion Formononetin might af-fect breast cancer cell proliferation and migration through modulation of HIF -1 α/CXCR4 signaling transduction.