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 different EGFR 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 groups: C group (control)

H group (HGF)

G group (gefitinib)

S group (SU11274)

GH group (gefitinib+HGF)

GSH group (gefitinib+SU11274+HGF). The cell survival was measured by MTT assay; the cell apoptosis was measured by flow 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 gefitinib. The cell survival when treating the HGF-induced cell lines with defferent concentration of gefitinib combined with SU11274 was significantly decreased than that when treating HGF-induced cell lines with gefitinib alone. In 3 cell lines

the apoptosis rate in HGS group was higher than that in HG group (P0.05). 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 (P0.05). Conclusion: SU11274 reversed gefitinib 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.