Abstract 1384: Prevention of angiogenesis by aldose reductase inhibition

Abstract

Abstract We have recently shown that Aldose Reductase (AR) known to be involved in oxidative stress-signaling, initiated by inflammatory markers, prevents human colon cancer cell growth in culture as well as in nude mice xenografts. Inhibition of AR also prevents azoxymethane-induced aberrant crypt foci formation in mice. In order to understand the chemopreventive mechanism of AR inhibition in colon cancer, we have investigated the role of AR in the mediation of angiogenic signals in vitro and in vivo models. Using human umbilical vein endothelial cells (HUVEC), we have investigated the effect of AR inhibition on VEGF- and bFGF- induced tube as well as spheroid formation in in vitro angiogenesis. We have also determined the invasion and migration of HUVEC by inhibition of AR. Further, to determine the in vivo efficacy of AR inhibition on angiogenesis, matrigel plug assay was performed using a rat model. Our results show that inhibition of AR significantly prevented the VEGF- and bFGF -induced proliferation and generation of reactive oxygen species in HUVEC. Further, AR inhibition also prevented the VEGF- and bFGF- induced secretion/expression of IL-6, MMP1, MMP9, ICAM, and VCAM. Matrigel plug model of angiogenesis in rats showed that inhibition of AR prevented the infiltration of blood cells, invasion, migration and formation of capillary like structures, and expression of blood vessels markers CD31 and vWF. Thus, our results demonstrate that AR inhibitors could be novel drugs for cancer chemoprevention by inhibiting angiogenesis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1384.