SNS-032 prevents tumor cell-induced angiogenesis by inhibiting vascular endothelial growth factor
SNS-032 prevents tumor cell-induced angiogenesis by inhibiting vascular endothelial growth factor
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DOI：
10.1593/neo.07136
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发表时间：
2007-05-01
期刊：
影响因子：
4.8
通讯作者：
Saha, Debabrata
中科院分区：
文献类型：
--
作者：
Ali, M. Aktar;Choy, Hak;Saha, Debabrata
内皮细胞的细胞增殖、迁移和毛细血管网络形成是血管生成的基本步骤，其涉及新血管的形成。本研究的目的是研究一种新的氨基噻唑SNS-032对这些关键步骤的体外血管生成使用的共培养系统组成的人脐静脉内皮细胞（HUVECs）和人胶质母细胞瘤细胞（U87 MG）。SNS-032是细胞周期蛋白依赖性激酶2、7和9的有效选择性抑制剂，并抑制转录和细胞周期。在这项研究中，我们检查了SNS-032存在下HUVEC和U87 MG细胞的增殖和活力，并观察到两种细胞系中细胞增殖的剂量依赖性抑制。SNS-032抑制内皮细胞的三维毛细血管网络形成。在共培养研究中，SNS-032完全阻止了U87 MG细胞介导的HUVEC毛细血管形成。这种抑制剂也阻止了HUVECs单独培养或与U87 MG细胞共培养时的迁移。此外，SNS-032显着防止生产的血管内皮生长因子（VEGF）在两种细胞系，而SNS-032是有效防止毛细血管网络的形成和迁移的内皮细胞时，活性重组VEGF添加到培养基中。总之，SNS-032阻止体外血管生成，并且该作用归因于VEGF的阻断。
Cell proliferation, migration, and capillary network formation of endothelial cells are the fundamental steps for angiogenesis, which involves the formation of new blood vessels. The purpose of this study is to investigate the effect of a novel aminothiazole SNS-032 on these critical steps for in vitro angiogenesis using a coculture system consisting of human umbilical vein endothelial cells ( HUVECs) and human glioblastoma cells ( U87MG). SNS-032 is a potent selective inhibitor of cyclin-dependent kinases 2, 7, and 9, and inhibits both transcription and cell cycle. In this study, we examined the proliferation and viability of HUVECs and U87MG cells in the presence of SNS-032 and observed a dose-dependent inhibition of cellular proliferation in both cell lines. SNS-032 inhibited three-dimensional capillary network formations of endothelial cells. In a coculture study, SNS-032 completely prevented U87MG cell-mediated capillary formation of HUVECs. This inhibitor also prevented the migration of HUVECs when cultured alone or cocultured with U87MG cells. In addition, SNS-032 significantly prevented the production of vascular endothelial growth factor ( VEGF) in both cell lines, whereas SNS-032 was less effective in preventing capillary network formation and migration of endothelial cells when an active recombinant VEGF was added to the medium. In conclusion, SNS-032 prevents in vitro angiogenesis, and this action is attributable to blocking of VEGF.