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

被引：25

作者：

Dao, Pascal ^{[1
]}

Jarray, Rafika ^{[1
]}

Smith, Nikaia ^{[1
]}

Lepelletier, Yves ^{[2
]}

Le Coq, Johanne ^{[3
]}

Lietha, Daniel ^{[3
]}

Hadj-Slimane, Reda ^{[4
]}

Herbeuval, Jean-Philippe ^{[1
]}

Garbay, Christiane ^{[1
]}

Raynaud, Francoise ^{[1
]}

Chen, Huixiong ^{[1
,5
]}

机构：

[1] Univ Paris 05, CNRS, Lab Chim & Biochim Pharmacol & Toxicol, UMR8601,UFR Biomed,PRES Sorbonne Paris Cite,CBNIT, F-75270 Paris 06, France

[2] Univ Paris 05, UMR CNRS 8147, PRES Sorbonne Paris Cite, Hop Necker, F-75743 Paris 15, France

[3] Spanish Natl Canc Res Ctr CNIO, Struct Biol & Biocomp Programme, Madrid 28029, Spain

[4] Visiotact Pharma, F-75012 Paris, France

[5] Guangdong Univ Technol, Sch Chem Engn & Light Ind, Educ Mega Ctr, Guangzhou 510006, Guangdong, Peoples R China

来源：

CANCER LETTERS | 2014年 / 348卷 / 1-2期

关键词：

FAK; FGFR2; Inhibitor; Angiogenesis; Cancer; TUMOR ANGIOGENESIS; ENDOTHELIAL FAK; CELL-SURVIVAL; CANCER-CELLS; IN-VITRO; CARCINOMA; EXPRESSION; THERAPY; TAE226; PROLIFERATION;

D O I：

10.1016/j.canlet.2014.03.007

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

FAK and FGFR2 signaling pathways play important roles in cancer development, progression and tumor angiogenesis. PHM16 is a novel ATP competitive inhibitor of FAR and FGFR2. To evaluate the therapeutic efficacy of this agent, we examined its anti-angiogenic effect in HUVEC and its anti-tumor effect in different cancer cell lines. We showed PHM16 inhibited endothelial cell viability, adherence and tube formation along with the added ability to induce endothelial cell apoptosis. This compound significantly delayed tumor cell growth. Together, these data showed that inhibition of both FAR and FGFR2 signaling pathways can enhance anti-tumor and anti-angiogenic activities. (C) 2014 Elsevier Ireland Ltd. All rights reserved.

引用

页码：88 / 99

页数：12

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