Abstract

背景与目的吲哚-3-甲醇(indole-3-carbinol, I3C)是十字花科蔬菜中一种主要的有效植物化学物质,且具有防癌和抗癌作用。本研究旨在观察I3C是否影响表皮生长因子受体(epidermal growth factor receptor, EGFR)表达水平不同的肺癌细胞放射敏感性。方法采用MTT和克隆形成实验方法分别检测肺癌细胞的生长和存活率;siRNA转染方法降低细胞中EGFR蛋白表达水平;Western blot和RT-PCR法分别测定EGFR蛋白和mRNA的表达。结果采用无明显毒副作用的5 μmol/L剂量的I3C预处理明显降低了EGFR表达阳性的人肺腺癌H1975和人肺鳞癌H226细胞对γ-射线照射的放射敏感性,而I3C对EGFR表达阴性的人肺鳞癌NIH-H520细胞的放射敏感性则影响非常小。Western blot结果显示I3C可以增加H1975和H226细胞中EGFR蛋白的表达水平和Y845位点磷酸化水平。EGFR siRNA降低了NIH-H1975细胞中EGFR蛋白的表达,增加了细胞的放射敏感性,并有效地降低和抑制了I3C导致的细胞耐辐射效应。结论我们的研究结果首次证实I3C可以通过调节EGFR表达和磷酸化水平从而影响肺癌细胞的放射治疗敏感性,提示EGFR可能是I3C影响肺癌放射治疗敏感性的重要靶蛋白。

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