The Mechanism Of C-MET Signal Pathway,Which Is Involved In HGF Induced Non-small Cell Lung Cancer Cells To Erlotinib Resistance

Purpose:To explore whether c-Met and its downstream signaling pathways participate in Erlotinib resistance induced by Hepatocyte growth factor (HGF)in different EGFR gene type of non-small cell lung cancer (NSCLC) cells.Methods:NSCLC cell lines with different EGFR gene types (PC9, H292, A549) were chosen and induced by HGF or (and) treated with Erlotinib. The experiment was divided into four groups:control, HGF, Erlotinib and HGF+Erlotinib groups. The cell proliferation was measured by MTT assay; the expressions of p-Met,c-Met, p-Stat3, Stat, p-Akt, Akt, p-Erkl/2 and Erkl/2 protein were examined by Western blot. Results:Erlotinib inhibited cell growth of three cell lines in a dose-dependent manner, the cell survival was increased when induced by HGF(P<0.05), and after down-regulation of c-Met, the cell survival showed no difference. HGF activated c-Met and its downstream signaling pathways protein quickly, and the expressions of p-Met, p-Stat3, p-Akt, p-Erkl/2 protein in HGF+Erlotinib group were higher than Erlotinib group,and after down-regulation of c-Met, showed no difference.Conclusion:HGF induces Erlotinib resistance in NSCLC with different EGFR gene types, mechanism.