Abstract 5099: Direct renin inhibitor attenuates rat hepatocarcinogenesis via anti-angiogenic activity

Direct renin inhibitor (DRI), aliskiren, is widely used as an anti-hypertensive agent in the clinical practice, and several reports have shown that renin plays an important role in several pathological processes. However, the role of renin in the hepatocarcinogenesis is still obscure. The aim of the current study was to examine the effect of DRI on the hepatocarcinogenesis in the rat model. Hepatocarcinogenesis model was induced in male F344 rats by the choline-deficient L-amino acid-defined diet for 12 weeks. The effect of DRI at clinically comparable low dose on the hepatocarcinogenesis was examined especially in conjunction with neovascularization. DRI exerted a marked inhibitory effect on the glutathione-S-transferase placental form (GST-P)-positive preneoplastic lesions along with suppression of the neovascularization in a dose-dependent manner. DRI also inhibited the hepatic expressions of angiotensin-II (AT-II), and vascular endothelial growth factor (VEGF). Our in vitro study showed that renin significantly augmented the in-vitro angiogenesis, whereas, interestingly, DRI did not inhibit the renin-induced the endothelial cell proliferation even at high dose. These results indicate that renin plays a pivotal role in hepatocarcinogenesis at least partly mediated by pro-angiogenic activity. Since DRI is already widely used in the clinical practice with safety, this drug may represent a potential new strategy against the hepatocarcinogenesis in the future. Citation Format: Yosuke Aihara, Hitoshi Yoshiji, Ryuichi Noguchi, Kosuke Kaji, Tadashi Namisaki, Kei Moriya, Mitsuteru Kitade, Hiroshi Fukui. Direct renin inhibitor attenuates rat hepatocarcinogenesis via anti-angiogenic activity. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5099. doi:10.1158/1538-7445.AM2013-5099