二甲双胍抑制Foxp3的表达诱导乳腺癌细胞凋亡

Metformin induced apoptosis in breast cancer cell by decreasing the expression of Foxp3

目的研究二甲双胍对于人乳腺癌细胞MCF-7增殖与调亡的效应,并探讨Foxp3在其中的作用。方法分别以二甲双胍(5mmol/L、10mmol/L、20mmol/L)干预人乳腺癌细胞MCF-7 48h后,采用MTT法检测细胞增殖抑制率;Hoechst33258染色和流式细胞仪分析细胞凋亡;实时(real-time)PCR检测Foxp3和caspase-3mRNA表达水平;Western blot法检测Foxp3蛋白的表达。结果与对照组(未经二甲双胍处理)相比,二甲双胍作用MCF-7细胞48h后,对细胞增殖有明显抑制作用(P<0.05);并可明显诱导MCF-7细胞凋亡,早期凋亡率分别为3.76%、8.96%和18.67%;经二甲双胍处理后,MCF-7细胞中caspase-3mRNA表达水平显著上调(P<0.05),而Foxp3mRNA和Foxp3蛋白表达水平降低(P<0.05)。结论二甲双胍有抑制MCF-7增殖并诱导其凋亡的作用,其机制可能与Foxp3表达下调有关。

Objective To research the effects of metformin on proliferation and apoptosis in human breast cancer MCF-7cells and investigate the role of Foxp3 in the effect.Methods The inhibit rate of MCF-7cells was measured by MTT assay after 48 h metformin treatment（5mmol/L、10mmol/L、20mmol/L）.Metformin-induced cell apoptosis was measured by Hoechst 33258 staining and flow cytometry.The expression levels of Foxp3 and caspase-3mRNA were detected by real-time PCR.Expression of Foxp3 protein was detected by Western blot.Results Metformin markedly inhibited proliferation of MCF-7（P〈0.05）compared with control group.And the early apoptotic rates increased to 3.76%,8.96%,and 18.67% with 5mmol/L、10mmol/L、20mmol/L metformin treatment,respectively.Metformin increased caspase-3mRNA expression levels,and decreased the expression levels of Foxp3 mRNA and protein expression levels（P〈0.05,vs.control）.Conclusion Metformin could inhibit the proliferation and induce apoptosis of MCF-7,and its mechanism maybe related to down-regulated expression of Foxp3.