HIF‐1 Inhibitor YC‐1 Reverses the Acquired Resistance of EGFR‐Mutant HCC827 Cell Line with MET Amplification to Gefitinib

Background Acquired resistance occurred in the majority of nonsmall cell lung cancer (NSCLC) patients receiving epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) therapy, and this may be related to the activation of the HIF-1 pathway. Therefore, we examined the influence of the hypoxia-inducible factor-1 (HIF-1) pathway inhibition on the sensitivity of HCC827 gefitinib-resistant (HCC827 GR) cells with MET amplification to gefitinib.Methods We established HCC827 GR cell line with MET amplification and set four groups with different treatment. An MTT assay, a colony formation analysis, and a wound healing assay were performed to determine the sensitivity change of HCC827 GR cells after different treatments. HIF-1 α , p-EGFR, and p-Met levels were detected with western blot. Correlations among HIF-1 α , p-EGFR, and p-Met levels of HCC827 GR cells with different treatments were analyzed with Pearson's correlation analysis.Results HIF-1 inhibitor YC-1 enhanced the sensitivity of HCC827 GR cells to gefitinib. p-Met level was correlated with HIF-1 α level, while there was no correlation between p-Met level and p-EGFR level.Conclusion HIF-1 inhibitor YC-1 is able to reverse the acquired resistance of HCC827 GR to gefitinib, and the regulation of the HIF-1 pathway on MET may be one of the mechanisms.