二甲双胍在结肠癌中通过抑制lncRNA-MALAT1的表达发挥抗肿瘤效应

Metformin antagonizes colon cancer by inhibiting the expression of lncRNA-MALAT1

目的探讨二甲双胍(MET)对结肠癌细胞的抑制作用及其机制。方法采用CCK-8、流式细胞术及Transwell检测MET对结肠癌细胞SW480和SW620增殖、凋亡及侵袭的影响,qRT-PCR检测5种lncRNA在结肠癌细胞中的表达,Western blotting检测MET和/或MALAT1基因敲减在体外对PI3K/AKT和ERK通路活性的影响。结果MET在体外对SW480和SW620细胞具有抑制作用,且呈剂量和时间依赖性(P<0.05)。MET可促进SW480和SW620细胞凋亡(P<0.05)。在5种lncRNA中,lncRNA-MALAT1在SW480和SW620细胞中的表达水平最高(P<0.01)。siRNA可抑制lncRNA-MALAT1表达,并进一步增强MET介导的抗结肠癌作用(P<0.05)。MET可下调结肠癌细胞中lncRNA-MALAT1的表达(P<0.05),并通过PI3K/AKT和ERK信号通路与lncRNAMALAT1敲减协同抑制结肠癌细胞的增殖和侵袭,并促进其凋亡(P<0.01)。结论MET在结肠癌细胞中通过抑制lncRNA-MALAT1的表达发挥抗肿瘤效应。

Objective To investigate the inhibiting effects of metformin on colon cancer cells and its mechanism.Methods CCK-8,flow cytometry and Transwell were used to detect the effects of MET on the proliferation,apoptosis and invasive ability of SW480 and SW620 colon cancer cells,and qRT-PCR method was employed to detect the expression of five lncRNAs in the two colon cancer cells.Western Blotting was applied to evaluate the effects of MET and/or lncRNAMALAT1knockdown on PI3K/Akt and ERK pathway activities in vitro.Results MET could inhibit the proliferation and promote the apoptosis of SW480 and SW620 cells in a dose-and time-dependent manner(P<0.05).Among the five lncRNAs,lncRNA-MALAT1 had the highest expression level in the SW480 and SW620 cells(P<0.01).The inhibition of lncRNAMALAT1 expression by siRNA could further enhance the anti colon cancer effect mediated by MET(P<0.05).MET could down-regulate the expression of lncRNA-MALAT1 in SW480 and SW620 cells(P<0.05),and further synergistically inhibit the proliferation,promote the apoptosis and suppress the invasive ability of SW480 and SW620 cells with the lncRNAMALAT1 knockdown via PI3K/Akt and ERK signaling pathways(P<0.01).Conclusion Metformin played an anti-cancer role through inhibiting the expression of lncRNA-MALAT1 in colon cancer.