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

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. 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-1α, p-EGFR, and p-Met levels were detected with western blot. Correlations among HIF-1α, p-EGFR, and p-Met levels of HCC827 GR cells with different treatments were analyzed with Pearson's correlation analysis. HIF-1 inhibitor YC-1 enhanced the sensitivity of HCC827 GR cells to gefitinib. p-Met level was correlated with HIF-1α level, while there was no correlation between p-Met level and p-EGFR level. 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. Copyright © 2021 Qian Jin et al.

Citation

Qian Jin, Jisheng Zheng, Ming Chen, Na Jiang, Xianrong Xu, Feihua Huang. HIF-1 Inhibitor YC-1 Reverses the Acquired Resistance of EGFR-Mutant HCC827 Cell Line with MET Amplification to Gefitinib. Oxidative medicine and cellular longevity. 2021;2021:6633867

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PMID: 33763171

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