p38激酶-HSP27信号通路在染料木黄酮诱导人乳腺癌细胞肌动蛋白细胞骨架解聚中的作用

The p38 kinase-HSP27 signaling pathway mediated the reorganization of actin cytoskeleton in breast cancer cells treated with genistein

目的:研究染料木黄酮(genistein)对人乳腺癌细胞(MDA-MB-435)肌动蛋白细胞骨架的影响,探讨p38激酶-HSP27信号通路对染料木黄酮诱导的细胞骨架肌动蛋白重组调控的可能机制。方法:不同浓度染料木黄酮(12.5、25.0、50.0和100.0μmol/L)体外孵育MDA-MB-435细胞24h后,用免疫印迹法研究细胞内p38激酶和HSP27表达及磷酸化水平的改变,同时分析肌动蛋白,HSP27其在细胞内定位的改变。结果:染料木黄酮处理24h,胞浆中的G-肌动蛋白含量明显增多,而细胞骨架中的F-肌动蛋白含量明显减少;p38激酶和HSP27的蛋白总量无明显改变,但二者磷酸化水平随着染料木黄酮处理浓度的增加逐渐降低;与此相应的是HSP27在胞浆中含量明显减少,在细胞骨架中含量明显增多。结论:p38激酶途径以及HSP27磷酸化/脱磷酸化过程可能介导染料木黄酮所致MDA-MB-435细胞肌动蛋白细胞骨架的重组。

Objective：To investigate the effects of genestin on the actin cytoskeleton and its mechanisms involeved in p38 kinase- HSP27 signaling pathway. Methods：The breast cancer cells（MDA-MB-435 cells） were treated with different concentrations of genis- tein （12.5,25.0,50.0 and 100.0 μmol/L） for 24 h. The expressions of p38 kinase and HSP27 and the phosphorylation of p38 and HSP27 were evaluated by Western blotting analysis. The expressions of actin and HSP27 in cytosolic fraction and cytoskeletal fraction were also detected by Western blotting. Results ：After treated with genistein for 24 h,cellular F-actin was depolymerized and the phosphorylation of p38 kinase and HSP27 was significantly attenuated compared with the control ceils. HSP27 translocated from the cytosolic fraction to the cytoskeletal fraction simultaneously. Conclusion：These findings suggested that the reorganization of actin cytoskeleton induced by genistein should probably be mediated by translocation of HSP27 in ceils via p38 kinase signaling pathway.