SU11274 reverse geiftinib resistance induced by hepatocyte growth factor in differentEGFR gene type of non-small cell lung cancer cells / 中国癌症杂志

ABSTRACT

Background and purpose:Hepatocyte growth factor (HGF) induce epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) resistance in non-small cell lung cancer (NSCLC) cells, the mechanism might be related with activation of c-Met. The present study aimed to explore whether c-Met inhibitor SU11274 reverse gefitinib resistance induced by HGF in differentEGFR gene types of NSCLC.Methods:PC9 (EGFR-activating mutant), H292 (EGFR-wild type) and A549 (EGFR-wiled) were chosen. The experiments were divided into 6 groupsC group (control), H group (HGF), G group (geiftinib), S group (SU11274), GH group (geiftinib+HGF), GSH group (geiftinib+SU11274+HGF). The cell survival was measured by MTT assay; the cell apoptosis was measured by lfow cytometry (FCM); the expressions of c-Met, Stat3, Akt and Erk1/2 protein were examined by Western blot.Results:Gefitinib inhibited cell growth of 3 cells lines in a dose-dependent manner, and treating with HGF could relieve inhibition of cell growth caused by geiftinib. The cell survival when treating the HGF-induced cell lines with defferent concentration of geiftinib combined with SU11274 was signiifcantly decreased than that when treating HGF-induced cell lines with geiftinib alone. In 3 cell lines, the apoptosis rate in HGS group was higher than that in HG group (P<0.05). In three cells lines, the p-Met, p-Stat3, p-Akt and p-Erk1/2 expressions in HGS group were lower than that in HG group (P<0.05).Conclusion:SU11274 reversed geiftinib resistance induced by HGF in different EGFR gene types of NSCLC cells, the mechanism might be related with inhibiting the HGF-induced activation of c-Met and its downstream signaling pathway.