和厚朴酚抑制结肠癌SW620细胞增殖与TGF-β1/p38 MAPK/Hippo信号传导的关系

Inhibitory growth effect of honokiol and TGF-β1/p38 MAPK/Hippo signaling pathway in human colon cancer cells

目的研究和厚朴酚(honokiol,HNK)对结肠癌SW620细胞的增殖抑制作用及其机制。方法采用结晶紫染色法、流式细胞术和Western blot等检测HNK抑制结肠癌SW620细胞增殖的作用,以及HNK对TGF-β1表达的影响;采用Western blot分析HNK对p38 MAPK磷酸化的影响,以及HNK联合应用过表达TGF-β1腺病毒与TGF-β1抑制剂对p38 MAPK磷酸化的影响;Western blot分析HNK对YAP磷酸化的影响,并分析HNK磷酸化p38 MAPK的作用与YAP的可能关系。结果HNK对SW620细胞增殖具有抑制作用,并能上调TGF-β1的蛋白表达;同时,HNK可以上调SW620细胞中p38 MAPK的磷酸化;过表达TGF-β1腺病毒能够促进p38 MAPK的磷酸化,而TGF-β1抑制剂能够抑制结论HNK能够抑制SW620细胞的增殖,其作用机制可能是通过上调TGF-β1并激活p38 MAPK信号通路来促进YAP磷酸化。

Aim To investigate the molecular mechanisms and inhibitory effect of honokiol(HNK)on the proliferation of colon cancer SW620 cells.Methods Crystal violet staining,flow cytometry and Western blot assays were used to for the detection of the effect of HNK on inhibiting the proliferation and promoting apoptosis on SW620 cells.Western blot was used to study the effect of HNK on the protein levels of TGF-β1 and analyze the effect of HNK on the phosphorylation of p38 MAPK,as well as the effect of HNK combined with exogenous adenoviruses of TGF-β1 and its inhibitor on the phosphorylation of p38 MAPK in SW620 cells.Western blot was also used to analyze the effect of HNK on the phosphorylation of YAP and analyze the possible relationship between HNK phosphorylation of p38 MAPK and YAP.Results HNK significantly inhibited the proliferation of SW620 cells and induced apoptosis,and up-regulated the expression levels of TGF-β1.Western blotting showed that HNK up-regulated the expression levels of phosphorylated p38 in SW620 cells.Meanwhile,HNK increased the protein levels of phosphorylated YAP.The exogenous adenoviruses of TGF-β1 and its inhibitor significantly enhanced or inhibited this effect,respectively.Conclusions HNK has obvious antiproliferative effect,which might be due to the up-regulation of TGF-β1 expression and up-regulation of phosphorylated YAP expression by activating the p38 MAPK signaling pathway.