白藜芦醇靶向EGFR和c-Met信号通路抑制非小细胞肺癌细胞增殖的机制

目的探讨白藜芦醇抑制非小细胞肺癌细胞增殖的分子机制。方法非小细胞肺癌细胞用白藜芦醇处理24、48和72 h,MTS和软琼脂集落形成实验检测白藜芦醇对非小细胞肺癌的抑制作用,免疫印迹检测白藜芦醇对表皮生长因子受体（epidermal growth factor receptor,EGFR）和肝细胞生长因子受体（c-Met）表达水平及下游信号通路的影响,流式细胞术检测白藜芦醇对细胞周期的影响。结果白藜芦醇剂量依赖性抑制非小细胞肺癌细胞的增殖。白藜芦醇抑制EGFR和c-Met信号通路磷酸化活化的同时下调了EGFR总蛋白及EGFR在胞膜和胞核的表达,同时降低了c-Met蛋白在胞膜的表达及c-Met蛋白...

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Published in肿瘤防治研究 Vol. 44; no. 1; pp. 11 - 16
Main Author 李伟 刘文斌 刘海丹
Format Journal Article
LanguageChinese
Published 2017
Subjects
白藜芦醇
肝细胞生长因子受体
表皮生长因子受体
非小细胞肺癌
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Summary:目的探讨白藜芦醇抑制非小细胞肺癌细胞增殖的分子机制。方法非小细胞肺癌细胞用白藜芦醇处理24、48和72 h,MTS和软琼脂集落形成实验检测白藜芦醇对非小细胞肺癌的抑制作用,免疫印迹检测白藜芦醇对表皮生长因子受体（epidermal growth factor receptor,EGFR）和肝细胞生长因子受体（c-Met）表达水平及下游信号通路的影响,流式细胞术检测白藜芦醇对细胞周期的影响。结果白藜芦醇剂量依赖性抑制非小细胞肺癌细胞的增殖。白藜芦醇抑制EGFR和c-Met信号通路磷酸化活化的同时下调了EGFR总蛋白及EGFR在胞膜和胞核的表达,同时降低了c-Met蛋白在胞膜的表达及c-Met蛋白60 kD大小剪切体在胞核的表达。白藜芦醇促进了A549细胞G_0/G_1期阻滞。结论白藜芦醇通过靶向EGFR和c-Met信号通路抑制非小细胞肺癌细胞的增殖。
Bibliography:42-1241/R
Objective To investigate the mechanism of resveratrol-mediated inhibition effect on human nonsmall cell lung cancer. Methods Non-small cell lung cancer cells were treated with various concentrations of resveratrol for 24, 48 and 72 h, the proliferation was evaluated by MTS and soft agar assay. Meanwhile, the activation of EGFR and c-Met signaling pathways after resveratrol treatment was tested via immunoblotting. The subcellular localization of EGFR and c-Met were assessed by Western blot. Flow cytometry was conducted to detect cell cycle progression. Results Resveratrol inhibited the proliferation of non-small cell lung cancer cells in a dose-dependent manner. Moreover, resveratrol treatment not only suppressed the phosphorylation of EGFR and c-Met signaling pathways, but also resulted in the down-regulation of total EGFR protein expression level, as well as its localization on membrane and in nucleus. Additionally, resveratrol treatment decreased c-Met expression on membrane and inhibited the 60 kD
ISSN:1000-8578