Overcoming the Intrinsic Gefitinib-resistance via Downregulation of AXL in Non-small Cell Lung Cancer
Journal of Cancer Prevention
; : 217-223, 2019.
Article
de En
| WPRIM
| ID: wpr-785916
Bibliothèque responsable:
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.
Mots clés
Texte intégral:
1
Indice:
WPRIM
Sujet Principal:
Protein-tyrosine kinases
/
Résistance aux substances
/
Régulation négative
/
Carcinome pulmonaire non à petites cellules
/
Récepteurs ErbB
/
Tumeurs du poumon
Type d'étude:
Prognostic_studies
Limites du sujet:
Humans
langue:
En
Texte intégral:
Journal of Cancer Prevention
Année:
2019
Type:
Article