Restoration of TRAIL-induced apoptosis in resistant human pancreatic cancer cells by a novel FAK inhibitor, PH11

被引：30

作者：

Dao, P. ^{[1
]}

Smith, N. ^{[1
]}

Scott-Algara, D. ^{[2
]}

Garbay, C. ^{[1
]}

Herbeuval, J. P. ^{[1
]}

Chen, H. ^{[1
]}

机构：

[1] Univ Paris 05, PRES Sorbonne Paris Cite, UFR Biomed, CBNIT,CNRS UMR8601, F-75270 Paris 06, France

[2] Inst Pasteur, Unite Regulat Infect Retrovir, F-75724 Paris, France

来源：

CANCER LETTERS | 2015年 / 360卷 / 01期

关键词：

Pancreatic cancer cell lines; TRAIL; FAK inhibitor; c-FLIP; PI3K/AKT pathway; FOCAL-ADHESION KINASE; C-FLIPL; RECEPTOR; SUPPRESSION; OVEREXPRESSION; KILLER/DR5; EXPRESSION; ANTITUMOR; PROTEINS; PATHWAYS;

D O I：

10.1016/j.canlet.2015.02.016

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

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. (C) 2015 Elsevier Ireland Ltd. All rights reserved.

引用

页码：48 / 59

页数：12

共 54 条

[1]

Asakuma J, 2003, CANCER RES, V63, P1365

[2]

DR5-mediated DISC controls caspase-8 cleavage and initiation of apoptosis in human glioblastomas [J].

Bellail, Anita C. ;

Tse, Margaret C. L. ;

Song, Jin H. ;

Phuphanich, Surasak ;

Olson, Jeffrey J. ;

Sun, Shi Yong ;

Hao, Chunhai .

JOURNAL OF CELLULAR AND MOLECULAR MEDICINE, 2010, 14 (06) :1303-1317

[3]

State of Art and Recent Developments of Anti-Cancer Strategies Based on TRAIL [J].

Bernardi, Stella ;

Secchiero, Paola ;

Zauli, Giorgio .

RECENT PATENTS ON ANTI-CANCER DRUG DISCOVERY, 2012, 7 (02) :207-217

[4]

Suppression of ultraviolet irradiation-induced apoptosis by overexpression of focal adhesion kinase in Madin-Darby canine kidney cells [J].

Chan, PC ;

Lai, JF ;

Cheng, CH ;

Tang, MJ ;

Chiu, CC ;

Chen, HC .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (38) :26901-26906

[5]

Cuello M, 2001, CANCER RES, V61, P4892

[6]

Integrins as Novel Drug Targets for Overcoming Innate Drug Resistance [J].

Damiano, Jason S. .

CURRENT CANCER DRUG TARGETS, 2002, 2 (01) :37-43

[7]

Design, Synthesis, and Evaluation of Novel Imidazo[1,2-a][1,3,5]triazines and Their Derivatives as Focal Adhesion Kinase Inhibitors with Antitumor Activity [J].

Dao, Pascal ;

Smith, Nikaia ;

Tornkiewicz-Raulet, Celine ;

Yen-Pon, Expedite ;

Carnacho-Artacho, Marta ;

Lietha, Daniel ;

Herbeuval, Jean-Phillipe ;

Commoul, Xavier ;

Garbay, Christiane ;

Chen, Huixiong .

JOURNAL OF MEDICINAL CHEMISTRY, 2015, 58 (01) :237-251

[8]

Inhibition of both focal adhesion kinase and fibroblast growth factor receptor 2 pathways induces anti-tumor and anti-angiogenic activities [J].

Dao, Pascal ;

Jarray, Rafika ;

Smith, Nikaia ;

Lepelletier, Yves ;

Le Coq, Johanne ;

Lietha, Daniel ;

Hadj-Slimane, Reda ;

Herbeuval, Jean-Philippe ;

Garbay, Christiane ;

Raynaud, Francoise ;

Chen, Huixiong .

CANCER LETTERS, 2014, 348 (1-2) :88-99

[9]

Synthesis of novel diarylamino-1,3,5-triazine derivatives as FAK inhibitors with anti-angiogenic activity [J].

Dao, Pascal ;

Jarray, Rafika ;

Le Coq, Johanne ;

Lietha, Daniel ;

Loukaci, Ali ;

Lepelletier, Yves ;

Hadj-Slimane, Reda ;

Garbay, Christiane ;

Raynaud, Francoise ;

Chen, Huixiong .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2013, 23 (16) :4552-4556

[10]

On the TRAIL to successful cancer therapy? Predicting and counteracting resistance against TRAIL-based therapeutics [J].

Dimberg, L. Y. ;

Anderson, C. K. ;

Camidge, R. ;

Behbakht, K. ;

Thorburn, A. ;

Ford, H. L. .

ONCOGENE, 2013, 32 (11) :1341-1350

← 1 2 3 4 5 6 →