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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
  • ISSN号:1000-8578
  • 期刊名称:《肿瘤防治研究》
  • 时间:0
  • 分类:R734.2[医药卫生—肿瘤;医药卫生—临床医学]
  • 作者机构:[1]中南大学附属湘雅二医院胸心外科,长沙410000, [2]中南大学附属湘雅三医院放射科,长沙410000, [3]湖南省肿瘤医院,中南大学湘雅医学院附属肿瘤医院病理科,长沙410000
  • 相关基金:国家自然科学基金(81401548)
中文摘要:

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。

英文摘要:

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 cleaved variant of c-Met translocated into nucleus. Flow cytometry data demonstrated that resveratrol induced cell cycle G_0/G_1 arrest. Conclusion Resveratrol inhibits human non-small cell lung cancer via directly targeting EGFR and c-Met signaling pathways.

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期刊信息
  • 《肿瘤防治研究》
  • 中国科技核心期刊
  • 主管单位:中华人民共和国卫生部
  • 主办单位:湖北省卫生厅 中国抗癌协会 湖北省肿瘤医院
  • 主编:魏少忠
  • 地址:武昌卓刀泉南路116号
  • 邮编:430079
  • 邮箱:zlfzyj@263.net.cn
  • 电话:027-87670126
  • 国际标准刊号:ISSN:1000-8578
  • 国内统一刊号:ISSN:42-1241/R
  • 邮发代号:38-70
  • 获奖情况:
  • 中国学术期刊综合评价数据库来源期刊,中国科学引文数据库来源期刊
  • 国内外数据库收录:
  • 美国化学文摘(网络版),英国农业与生物科学研究中心文摘,波兰哥白尼索引,美国剑桥科学文摘,日本日本科学技术振兴机构数据库,中国中国科技核心期刊,中国北大核心期刊(2004版),中国北大核心期刊(2008版),中国北大核心期刊(2011版),中国北大核心期刊(2014版)
  • 被引量:17449