Tetrandrine Increases the Sensitivity of Human Lung Adenocarcinoma PC14 Cells to Gefitinib by Lysosomal Inhibition.
Anticancer Res
; 39(12): 6585-6593, 2019 Dec.
Article
en En
| MEDLINE
| ID: mdl-31810924
BACKGROUND/AIM: Human lung adenocarcinoma PC14 cells without mutations in the epidermal growth factor receptor (EGFR) are less sensitive to gefitinib than PC9 cells with EGFR mutations. We report the involvement of tetrandrine in autophagy flux as a mechanism that enhances the sensitivity of PC14 cells to gefitinib. MATERIALS AND METHODS: Sensitivity to gefitinib was determined by a growth inhibition assay, and quantitative real-time PCR, western blotting, and fluorescent immunostaining were used to detect autophagy. RESULTS: In PC14 cells, combined treatment with gefitinib and tetrandrine caused a significant increase in gefitinib sensitivity and autophagy-related mRNAs and proteins (LC3, etc.), and the LC3 protein accumulated in lysosomes. Furthermore, an autophagy flux assay revealed that tetrandrine inhibited lysosomes and that gefitinib promoted autophagy. Finally, the sensitivity of PC14 cells to gefitinib was enhanced with chloroquine. CONCLUSION: Tetrandrine possibly increases the susceptibility of PC14 cells to gefitinib by lysosomal inhibition.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Bencilisoquinolinas
/
Gefitinib
/
Adenocarcinoma del Pulmón
/
Neoplasias Pulmonares
/
Lisosomas
/
Proteínas Asociadas a Microtúbulos
Tipo de estudio:
Diagnostic_studies
Límite:
Humans
Idioma:
En
Revista:
Anticancer Res
Año:
2019
Tipo del documento:
Article
País de afiliación:
Japón
Pais de publicación:
Grecia