TY - JOUR T1 - Suppression of Renin-Angiotensin System Attenuates Hepatocarcinogenesis <em>Via</em> Angiogenesis Inhibition in Rats JF - Anticancer Research JO - Anticancer Res SP - 3335 LP - 3340 VL - 25 IS - 5 AU - HITOSHI YOSHIJI AU - RYUICHI NOGUCHI AU - SHIGEKI KURIYAMA AU - JUNICHI YOSHII AU - YASUHIDE IKENAKA AU - KOJI YANASE AU - TADASHI NAMISAKI AU - MITSUTERU KITADE AU - MASAHARU YAMAZAKI AU - MASAHITO UEMURA AU - HIROSHI FUKUI Y1 - 2005/09/01 UR - http://ar.iiarjournals.org/content/25/5/3335.abstract N2 - Recent studies have shown that the renin-angiotensin system (RAS) as well as angiogenesis is involved in tumor development. The aim of the present study was to examine the interaction of RAS, angiogenesis and a potent angiogenic factor, namely the vascular endothelial growth factor (VEGF), in the hepatocarcinogenesis process. In a diethylnitrosamine-induced rat hepatocarcinogenesis model, a clinically used angiotensin-converting enzyme inhibitor, perindopril (PE), significantly suppressed glutathione S-transferase placental form (GST-P)-positive preneoplastic lesions along with inhibition of neovascularization in the liver. The hepatic expression of VEGF was also attenuated. The degree of angiogenesis correlated well with the development of preneoplastic lesions. Our in vitro study showed that PE significantly suppressed VEGF-induced tubular formation and the migration of endothelial cells (EC), whereas it did not affect the proliferation of EC. These results suggested that RAS plays an important role in hepatocarcinogenesis, at least partly through VEGF-mediated angiogenesis. Copyright© 2005 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved ER -