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Growth Suppression in Lung Cancer Cells Harboring EGFR-C797S Mutation by Quercetin

Authors :
Kuo-Yen Huang
Tong-Hong Wang
Chin-Chuan Chen
Yann-Lii Leu
Hsin-Jung Li
Cai-Ling Jhong
Chi-Yuan Chen
Source :
Biomolecules, Vol 11, Iss 9, p 1271 (2021)
Publication Year :
2021
Publisher :
MDPI AG, 2021.

Abstract

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are approved treatments for non-small-cell lung cancer (NSCLC) patients harboring activating EGFR mutations. The EGFR C797S mutation is one of the known acquired-resistance mutations to the latest third-generation TKIs. At present, there are no clear options for treating patients who acquire resistance to third-generation TKIs. The acquisition of the EGFR C797S mutation was shown to upregulate the expression of AXL, a receptor tyrosine kinase of the TAM (TYRO3-AXL-MER) family, and the suppression of AXL is effective in reducing the growth of NSCLC cells harboring EGFR C797S. As quercetin was recently shown to inhibit AXL, quercetin may be effective in treating NSCLC cells harboring the EGFR C797S mutation. In this work, the cytotoxic effects of quercetin and its ability to inhibit tumor growth were examined in TKI-resistant NSCLC cells harboring the EGFR C797S mutation. We demonstrated that quercetin exhibited potent cytotoxic effects on NSCLC cells harboring the EGFR C797S mutation by inhibiting AXL and inducing apoptosis. Quercetin inhibited the tumor growth of xenografted NSCLC cells harboring the EGFR C797S mutation and appeared to act synergistically with brigatinib to inhibit of tumor growth in vivo. In summary, herein, we revealed that quercetin is an effective inhibitor for the treatment of non-small-cell lung cancer harboring the EGFR C797S mutation.

Details

Language :
English
ISSN :
2218273X
Volume :
11
Issue :
9
Database :
Directory of Open Access Journals
Journal :
Biomolecules
Publication Type :
Academic Journal
Accession number :
edsdoj.51e8c23c27ee4e349820f36017f61f2f
Document Type :
article
Full Text :
https://doi.org/10.3390/biom11091271