Restoration of TRAIL-induced apoptosis in resistant human pancreatic cancer cells by a novel FAK inhibitor, PH11.
Cancer Lett
; 360(1): 48-59, 2015 Apr 28.
Article
en En
| MEDLINE
| ID: mdl-25684663
ABSTRACT
Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) emerges as one of the most-promising experimental cancer therapeutic drugs and is currently being tested in clinical trials. However, both intrinsic and acquired resistance of human cancer cells to TRAIL-induced apoptosis poses a huge problem in establishing clinically efficient TRAIL therapies. To assess the regulation of TRAIL-resistance in human pancreatic cancer cells, we studied the TRAIL resistant pancreatic cell line PANC-1. We show that treatment with PH11, a novel Focal Adhesion Kinase (FAK) inhibitor in association with TRAIL rapidly induces apoptosis in TRAIL-resistant PANC-1 cells, but not in normal human fibroblast cells. To explain sensitization, we showed that PH11 restores TRAIL apoptotic pathway in PANC-1 cells through down-regulation of c-FLIP via inhibition of FAK and the phosphatidylinositol-3 kinase (PI3K)/AKT pathways. These findings suggest that this combined treatment may offer an attractive therapeutic strategy for safely and efficiently treating pancreatic cancer.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Neoplasias Pancreáticas
/
Triazinas
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Apoptosis
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Resistencia a Antineoplásicos
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Inhibidores de Proteínas Quinasas
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Quinasa 1 de Adhesión Focal
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Ligando Inductor de Apoptosis Relacionado con TNF
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Imidazoles
/
Antineoplásicos
Límite:
Humans
Idioma:
En
Revista:
Cancer Lett
Año:
2015
Tipo del documento:
Article
País de afiliación:
Francia