Yoshiji Hitoshi, Noguchi Ryuichi, Kuriyama Shigeki, Yoshii Junichi, Ikenaka Yasuhide, Yanase Koji, Namisaki Tadashi, Kitade Mitsuteru, Yamazaki Masaharu, Uemura Masahito, Fukui Hiroshi
Third Department of Internal Medicine, Nara Medical University, Nara, Japan.
Anticancer Res. 2005 Sep-Oct;25(5):3335-40.
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.
近期研究表明，肾素-血管紧张素系统（RAS）以及血管生成均参与肿瘤发展。本研究的目的是探讨RAS、血管生成以及一种强效血管生成因子，即血管内皮生长因子（VEGF）在肝癌发生过程中的相互作用。在二乙基亚硝胺诱导的大鼠肝癌发生模型中，一种临床使用的血管紧张素转换酶抑制剂培哚普利（PE）显著抑制了谷胱甘肽S-转移酶胎盘型（GST-P）阳性的癌前病变，同时抑制了肝脏中的新生血管形成。VEGF的肝脏表达也减弱。血管生成程度与癌前病变的发展密切相关。我们的体外研究表明，PE显著抑制VEGF诱导的管状结构形成和内皮细胞（EC）迁移，而不影响EC的增殖。这些结果提示，RAS在肝癌发生中起重要作用，至少部分是通过VEGF介导的血管生成实现的。
