迷迭香酸通过Traf6/TAK1信号通路调控胃癌细胞的增殖及凋亡

Regulation of rosmarinic acid on proliferation and apoptosis of human gastric cancer cell via Traf6/TAK1 signaling pathway

[目的]观察迷迭香酸对胃癌细胞(HGC27)增殖、凋亡的作用效应及对Traf6/TAK1信号通路的影响。[方法]体外培养HGC27细胞,采用低(25μmol/L)、中(50μmol/L)、高(100μmol/L)剂量迷迭香酸干预,然后运用CCK8法检测HGC27细胞增殖情况,流式细胞术分析HGC27细胞周期及凋亡情况,Western Blot技术检测凋亡蛋白Bax、Bcl-2表达及肿瘤坏死相关受体因子6/转化生长因子活化蛋白激酶1(Traf6/TAK1)信号通路活化情况。[结果]与对照组相比,不同剂量迷迭香酸能明显抑制HGC27细胞增殖、诱导其凋亡,将HGC27细胞停留在G0/G1期,差异相比有统计学意义(P<0.05);与对照组相比,不同浓度迷迭香酸可以明显诱导Bax表达,显著抑制Bcl-2、Traf6及p-TAK1蛋白表达,差异相比有统计学意义(P<0.05)。[结论]迷迭香酸可将HGC27细胞停留在G0/G1期,抑制其增殖、诱导凋亡,其作用机制可能与抑制Traf6/TAK1信号通路活化相关。

[Objective]To observe the effects of rosmarinic acid on proliferation and apoptosis of human gastric cancer cell(HGC27),and to investigate the impact of rosmarinic acid on the activation of Traf6/TAK1 signaling pathway.[Methods]HGC27 cells were cultured in vitro and supplemented with low-(25μmol/L),middle-(50μmol/L)and high-(100μmol/L)dose rosmarinic acid.CCK8 assay was used to detect the HGC27 cells proliferation.Flow cytometry was used to measure the cell cycle and apoptosis of HGC27 cells.Western Blot was used to determine the expression levels of Bax,Bcl-2 and the activation of tumor necrosis factor receptor related factor of 6/transforming growth factor-activated kinase-1(Traf6/TAK1)signaling pathway.[Results]Compared with control group,varying concentrations of rosmarinic acid can greatly inhibit the proliferation of HGC27 cells and induce the apoptosis of HGC27 cells via remaining cells in G0/G1 phase(P<0.05).Compared with control group,varying concentrations of rosmarinic acid can greatly induce the expression level of Bax and suppress the expression levels of Bcl-2,Traf6 and p-TAK1(P<0.05).[Conclusion]Rosmarinic acid can stay the HGC27 cells in G0/G1 and inhibit proliferation and induce apoptosis,which mechanism may be related to the inhibition of Traf6/TAK1 signaling pathway.