Overcoming the Intrinsic Gefitinib-resistance via Downregulation of AXL in Non-small Cell Lung Cancer
Journal of Cancer Prevention
; : 217-223, 2019.
Article
in En
| WPRIM
| ID: wpr-785916
Responsible library:
WPRO
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.
Key words
Full text:
1
Index:
WPRIM
Main subject:
Protein-Tyrosine Kinases
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Drug Resistance
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Down-Regulation
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Carcinoma, Non-Small-Cell Lung
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ErbB Receptors
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Lung Neoplasms
Type of study:
Prognostic_studies
Limits:
Humans
Language:
En
Journal:
Journal of Cancer Prevention
Year:
2019
Type:
Article