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HGF-induced resistance to erlotinib in EGFR-mutated and EGFR wildtype non-small lung cancer cells in vitro
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Abstract:
Objective: To assess differences in erlotinib resistance between EGFR-mutated and EGFR wildtype non-small lung cancer (NSCLC) cells following hepatocyte growth factor (HGF) in vitro. Methods: EGFR-mutated NSCLC PC9 cells and EGFR-wild type NSCLC H292 and A549 cells were left untreated (control) or treated with HGF, erlotinib or HGF plus erlotinib. Cell viability was assessed by MTT assays, cell appotosis and cell cycle progression by flow cytomety and protein contents of c-Met, EGFR and ErbB3 by Western blotting. Results: Erlotinib resulted in a significant proliferation inhibition in all three types of NSCLS cells in a dose-dependent manner and HGF effectively attenuated the erlotinib-induced proliferation inhibition. In all three types of cells studied, the apoptosis rate in the combination treatment (HGF plus erlotinib) group was lower than that in the erlotinib group (P<0.05), and erlotinib induced G1 arrest. In H292 and A549 cells, the proportion of cells at G0/G1 phase was significantly lower in the combination treatment group than in the erlotinib group (P<0.05). Protein content of c-Met was significantly higher in the combination treatment than in the erlotinib group (P<0.05) whereas protein contents of p-EGFR and p-ErbB3 were not different between treatment groups (P>0.05) in all three types of cells. Conclusion: HGF may induce erlotinib resistance differentially in EGFR wildtype and EGFR-mutated NSCLC cells, possibly an Met activation-dependent mechanism.
Keywords:
hepatocyte growth factor(HGF) ; erlotinib ; non-small lung cancer(NSCLC) ; c-Met ; resistance
Project Supported:
Project supported by the National Natural Science Foundation of China (No. 81160291)
