Overcoming the Intrinsic Gefitinib-resistance via Downregulation of AXL in Non-small Cell Lung Cancer
10.15430/JCP.2019.24.4.217
- Author:
Inae JEONG
1
;
Jayoung SONG
;
Song Yi BAE
;
Sang Kook LEE
Author Information
1. College of Pharmacy, Seoul National University, Seoul, Korea. sklee61@snu.ac.kr
- Publication Type:Original Article
- Keywords:
axl receptor tyrosine kinase;
Non-small-cell lung cancer;
Gefitinib;
Yuanhuadine;
Drug resistance
- MeSH:
Carcinoma, Non-Small-Cell Lung;
Down-Regulation;
Drug Resistance;
Humans;
Lung Neoplasms;
Protein-Tyrosine Kinases;
Receptor, Epidermal Growth Factor
- From:Journal of Cancer Prevention
2019;24(4):217-223
- CountryRepublic of Korea
- Language:English
-
Abstract:
BACKGROUND: Resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), such as gefitinib, is a limited factor in the treatment of non-small-cell lung cancer (NSCLC) patients. Therefore, ongoing studies are trying to identify EGFR-TKIs-resistant mechanisms and to discover novel therapeutic strategies and targets for NSCLC treatment.METHODS: In the present study, the possibility of overcoming intrinsic gefitinib-resistance was examined by regulating the expression of AXL. A natural product-derived antitumor agent, yuanhuadine (YD) was employed to modulate the expression of AXL in the cells.RESULTS: Treatment with YD effectively downregulated AXL expression in AXL-overexpressed gefitinib-resistant H1299 cells. The combination of gefitinib and YD exhibited a synergistic grwoth-inhibitory activity in H1299 cells by downregulation of AXL expression.CONCLUSIONS: Based on these findings, AXL was found to be a promising therapeutic target to overcome the intrinsic resistance to gefitinib in NSCLC. Furthermore, YD is able to effectively regulate the expression of AXL and thus it may be applicable as a potential lead compound for the treatment of gefitinib-resistant NSCLC.
