Endostar, a novel recombinant human endostatin, exerts antiangiogenic effect via blocking VEGF-induced tyrosine phosphorylation of KDR/Flk-1 of endothelial cells
Endostar, a novel recombinant human endostatin, exerts antiangiogenic effect via blocking VEGF-induced tyrosine phosphorylation of KDR/Flk-1 of endothelial cells
复制标题
DOI：
10.1016/j.bbrc.2007.06.155
复制
发表时间：
2007-09-14
影响因子：
3.1
通讯作者：
Guo, Qing-Long
中科院分区：
文献类型：
--
作者：
Ling, Yun;Yang, Yong;Guo, Qing-Long
恩度是一种在大肠杆菌中表达和纯化的新型重组人内皮抑素，其附加九个氨基酸序列并形成另一个组氨酸标签结构，于2005年被国家食品药品监督管理局批准用于治疗非小细胞肺癌。但其作用机制此前尚未阐明。在这项研究中，我们检查了恩度的体外和体内抗血管生成活性。结果表明，恩度在体外抑制了 VEGF 刺激的人脐静脉内皮细胞 (HUVEC) 的增殖、迁移和管形成。恩度在体外阻断大鼠主动脉环萌发的微血管。此外，在鸡绒毛尿囊膜（CAM）测定中，它可以抑制现有血管形成新的毛细血管，并影响肿瘤中血管的生长。我们进一步发现恩度的抗血管生成作用与 VEGF 触发的信号传导相关。恩度抑制 VEGF 诱导的 KDR/Flk-1 (VEGFR-2) 酪氨酸磷酸化以及 HUVEC 中 VEGFR-2 的整体表达以及 ERK、p38、MAPK 和 AKT 的激活。总的来说，这些数据表明了恩度和 VEGF 信号通路之间的关系，并为恩度的抗血管生成作用提供了分子基础。 (c) 2007 Elsevier Inc. 保留所有权利。
Endostar, a novel recombinant human endostatin expressed and purified in Escherichia coli with an additional nine-amino acid sequence and forming another his-tag structure, was approved by the SFDA in 2005 for the treatment of non-small-cell lung cancer. But its mechanism of action has not been illustrated before. In this study, we examined the antiangiogenic activities of endostar in vitro and in vivo. The results showed that endostar suppressed the VEGF-stimulated proliferation, migration, and tube formation of human umbilical vein endothelial cells (HUVECs) in vitro. Endostar blocked microvessel sprouting from rat aortic rings in vitro. Moreover, it could inhibit the formation of new capillaries from pre-existing vessels in the chicken chorioallantoic membrane (CAM) assay and affect the growth of vessels in tumor. We further found the antiangiogenic effects of endostar were correlated with the VEGF-triggered signaling. Endostar suppressed the VEGF-induced tyrosine phosphorylation of KDR/Flk-1(VEGFR-2) as well as the overall VEGFR-2 expression and the activation of ERK, p38, MAPK, and AKT in HUVECs. Collectively, these data indicated the relationship between endostar and VEGF signal pathways and provided a molecular basis for the antiangiogenic effects of endostar. (c) 2007 Elsevier Inc. All rights reserved.