CNRS, UMR8601, Laboratoire de Chimie et Biochimie Pharmacologiques et Toxicologiques, CBNIT, Université Paris Descartes, PRES Sorbonne Paris Cité, UFR Biomédicale, 45 rue des Saints-Pères, 75270 Paris Cedex 06, France.
UMR CNRS 8147, Université Paris Descartes, PRES Sorbonne Paris Cité, Hôpital Necker, 149, rue de Sèvre, 75743 Paris Cedex 15, France.
Cancer Lett. 2014 Jun 28;348(1-2):88-99. doi: 10.1016/j.canlet.2014.03.007. Epub 2014 Mar 19.
FAK and FGFR2 signaling pathways play important roles in cancer development, progression and tumor angiogenesis. PHM16 is a novel ATP competitive inhibitor of FAK 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 FAK and FGFR2 signaling pathways can enhance anti-tumor and anti-angiogenic activities.
FAK 和 FGFR2 信号通路在癌症的发生、发展和肿瘤血管生成中起着重要作用。PHM16 是一种新型的 FAK 和 FGFR2 的 ATP 竞争性抑制剂。为了评估该药物的治疗效果，我们研究了它在 HUVEC 中的抗血管生成作用及其在不同癌细胞系中的抗肿瘤作用。结果表明，PHM16 抑制内皮细胞活力、黏附和管腔形成，并具有诱导内皮细胞凋亡的能力。该化合物显著延迟了肿瘤细胞的生长。综上所述，这些数据表明抑制 FAK 和 FGFR2 信号通路均可增强抗肿瘤和抗血管生成活性。
