中国肺癌杂志Issue(9)：464-469,6.DOI:10.3779/j.issn.1009-3419.2013.09.05
c-Met信号通道参与HGF诱导不同基因型非小细胞肺癌细胞株对吉非替尼耐药
c-Met Signaling Pathway Participating in the Geiftinib Resistance of Different Gene Types of Non-small Cell Lung Cancer Cells Induced by HGF In Vitro
摘要
Abstract
Background and objective It has been known that hepatocyte growth factor (HGF) induces geiftinib resistance in non-small cell lung cancer (NSCLC) cells. hTe possible mechanism may be related to the activation of the HGF receptor c-Met. hTe aim of this study is to investigate the involvement of c-Met and its downstream signaling pathway in the HGF-induced geiftinib resistance of NSCLC cells with different epidermal growth factor receptor (EGFR) gene types. Meth-ods NSCLC cell lines with different EGFR genes (PC-9, PC9/R, H292, and A549) were selected and induced by HGF. Cell survival was determined by MTT assay and the expression of Met and downstream signaling proteins were examined by West-ern blot. Results Geiftinib inhibited the cell growth of PC9, H292, and A549 cell lines in a dose-dependent manner. hTe con-centration-survival curve notably shitfed to the right when induced by HGF. hTe apoptotic rate was lower when the cells were treated with HGF and geiftinib than when these cells were treated with geiftinib alone (P<0.05), particularly in PC9, H292, and A549 cells, but not in PC9/R. HGF stimulated the phosphorylation of Met and downstream signaling proteins in PC9, H292, PC9/R, and A549 cell lines. p-Met, p-Akt, p-Stat3, and p-Erk1/2 expressions were higher when the cells were treated with HGF and geiftinib than when these cells were treated with geiftinib alone, particularly in PC9, H292, and A549 cells, but not in PC9/R. Conclusion c-Met and its downstream signaling pathway possibly participated in the HGF-induced geiftinib resistance in NSCLC cells with different EGFR gene types.关键词
肝细胞生长因子/吉非替尼/c-Met/耐药/肺肿瘤Key words
HGF/Geiftinib/c-Met/Resistance/Lung neoplasm引用本文复制引用
玄香兰,安昌善,周彩存..c-Met信号通道参与HGF诱导不同基因型非小细胞肺癌细胞株对吉非替尼耐药[J].中国肺癌杂志,2013,(9):464-469,6.基金项目
本研究受国家自然科学基金项目（No.81160291）、吉林省自然科学基金项目（No.201015247）资助 （）
