STI-571 inhibits in vitro angiogenesis

被引：14

作者：

Dudley, A

Gilbert, RE ^{[1
]}

Thomas, D

Cox, A

Price, JT

Best, J

Jenkins, A

机构：

[1] Univ Melbourne, St Vincents Hosp, Dept Med, Parkville, Vic 3052, Australia

[2] St Vincents Inst Med Res, Melbourne, Vic, Australia

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2003年 / 310卷 / 01期

关键词：

STI-571; angiogenesis; aortic ring assay;

D O I：

10.1016/j.bbrc.2003.08.129

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Compounds that block angiogenesis are effective in the treatment of certain cancers and other angiogenesis-related diseases. Many of these compounds specifically target the rapidly proliferating and migrating endothelial cell. However, angiogenesis is a multi-faceted process involving heterotypic interactions between various cell types. For example, PDGFBB is an important cytokine secreted by endothelial cells that attracts smooth muscle cells to surround and stabilize a nascent vessel. Therefore, we hypothesized that STI-571. a tyrosine kinase inhibitor with PDGFbeta receptor activity, would inhibit angiogenesis through an anti-migratory effect on smooth muscle cells. We demonstrate that STI-571 completely inhibits in vitro angiogenesis in fibrinogen-embedded mouse aorta. Furthermore, this angiostatic property was due mainly to an anti-migratory and anti-proliferative effect upon smooth muscle cells. These data suggest that STI-571, in addition to its efficacy in the treatment of certain cancers, may also prove to be clinically useful in diseases characterized by unregulated angiogenesis. (C) 2003 Elsevier Inc. All rights reserved.

引用

页码：135 / 142

页数：8

共 34 条

[1] Chronic myelogenous leukemia in T cell lymphoid blastic phase achieving durable complete cytogenetic and molecular remission with imatinib mesylate (STI571; Gleevec) therapy [J].