Examining the role of Rac1 in tumor angiogenesis and growth: a clinically relevant RNAi-mediated approach

被引：32

作者：

Vader, P. ^{[2
]}

van der Meel, R. ^{[2
]}

Symons, M. H. ^{[3
]}

Fens, M. H. A. M. ^{[2
]}

Pieters, E. ^{[2
]}

Wilschut, K. J. ^{[2
]}

Storm, G. ^{[2
]}

Jarzabek, M. ^{[1
]}

Gallagher, W. M. ^{[4
]}

Schiffelers, R. M. ^{[2
]}

Byrne, A. T. ^{[1
]}

机构：

[1] Royal Coll Surgeons Ireland, Dept Physiol & Med Phys, Dublin 18, Ireland

[2] Univ Utrecht, Dept Pharmaceut, Utrecht Inst Pharmaceut Sci, Fac Sci, NL-3584 CG Utrecht, Netherlands

[3] Feinstein Inst Med Res N Shore LIJ, Ctr Oncol & Cell Biol, Manhasset, NY 11030 USA

[4] Univ Coll Dublin, UCD Sch Biomol & Biomed Sci, UCD Conway Inst, Dublin 4, Ireland

来源：

ANGIOGENESIS | 2011年 / 14卷 / 04期

基金：

爱尔兰科学基金会;

关键词：

Rho GTPases; Rac1; RNA interference; siRNA; Tumor angiogenesis; RHO-GTPASES; ENDOTHELIAL-CELLS; LUMEN FORMATION; BREAST-CANCER; IN-VIVO; TUMORIGENESIS; NANOPARTICLES; METASTASIS; DELIVERY; INVASION;

D O I：

10.1007/s10456-011-9229-x

中图分类号：

R6 [外科学];

学科分类号：

1002 ; 100210 ;

摘要：

Angiogenesis, the sprouting of new blood vessels from the pre-existing vasculature, is a well established target in anti-cancer therapy. It is thought that the Rho GTPase Rac1 is required during vascular endothelial growth factor (VEGF)-mediated angiogenesis. In the present study, we have used a clinically relevant RNA interference approach to silence Rac1 expression. Human umbilical vein endothelial cells were transiently transfected with non-specific control siRNA (siNS) or Rac1 siRNA (siRac1) using electroporation or Lipofectamine 2000. Functional assays with transfected endothelial cells were performed to determine the effect of Rac1 knockdown on angiogenesis in vitro. Silencing of Rac1 inhibited VEGF-mediated tube formation, cell migration, invasion and proliferation. In addition, treatment with Rac1 siRNA inhibited angiogenesis in an in vivo Matrigel plug assay. Intratumoral injections of siRac1 almost completely inhibited the growth of grafted Neuro2a tumors and reduced tumor angiogenesis. Together, these data indicate that Rac1 is an important regulator of VEGF-mediated angiogenesis. Knockdown of Rac1 may represent an attractive approach to inhibit tumor angiogenesis and growth.

引用

页码：457 / 466

页数：10

共 37 条

[21] Rho GTPases: Biochemistry and biology [J].