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

Overview

Journal Oxid Med Cell Longev

Publisher Wiley

Specialties Cell Biology
Endocrinology

Date 2021 Mar 25

PMID 33763171

Citations 3

Authors

Qian Jin

Jisheng Zheng

Ming Chen

Na Jiang

Xianrong Xu

Feihua Huang

Affiliations

Soon will be listed here.

Abstract

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, p-EGFR, and p-Met levels were detected with western blot. Correlations among HIF-1, 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 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.

Citing Articles

Current Landscape of Therapeutic Resistance in Lung Cancer and Promising Strategies to Overcome Resistance.

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Targeting HIF-1α by Natural and Synthetic Compounds: A Promising Approach for Anti-Cancer Therapeutics Development.

Ghosh R, Samanta P, Sarkar R, Biswas S, Saha P, Hajra S Molecules. 2022; 27(16).

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Angiogenic activities are increased via upregulation of HIF-1α expression in gefitinib-resistant non-small cell lung carcinoma cells.

Cha J, Bae W, Choi J, Lee S, Jeong J Oncol Lett. 2021; 22(3):671.

PMID: 34345296 PMC: 8323004. DOI: 10.3892/ol.2021.12932.

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