Third Department of Internal Medicine, Nara Medical University, Kashihara, Nara, Shijo-cho 840, Kashikan, Nara 634-8522, Japan.
Curr Cancer Drug Targets. 2011 May;11(4):431-41. doi: 10.2174/156800911795538084.
Angiogenesis is a complex and critical process essential for supporting the growth of hepatocellular carcinoma (HCC) as well as hepatocarcinogenesis. Recent studies have revealed that renin-angiotensin system (RAS) is involved in many types of cancer including HCC. Some studies have proven that suppression of angiotensin-II (AT-II) by a clinically used angiotensin-converting enzyme inhibitor (ACE-I) significantly attenuated the HCC growth and hepatocarcinogenesis along with down-regulation of a potent angiogenic factor; namely, the vascular endothelial growth factor (VEGF). When used in combination with the clinical available drugs such as interferon (IFN) and vitamin K (VK), ACE-I exerted more potent anti-tumor activities as compared with either single agent in addition to suppression of the intra-tumoral angiogenesis both in experimental models and clinical practice. It is well known that AT-II plays an important role in the insulin resistance (IR), and IR is reportedly involved in the progression of HCC. The combination of ACE-I and branched-chain amino acids (BCAA) exerted a marked chemopreventive effect against HCC under the condition of IR. In addition to AT-II, aldosterone (Ald), which plays a role in the downstream of AT-II, is also involved in the HCC development, and a clinically used selective Ald blocker (SAB) significantly suppressed the HCC growth and hepatocarcinogenesis. Since ACE-I, IFN, VK, BCAA, and SAB are already in widespread clinical use without any serious adverse effects, they may represent a potential new strategy for cancer therapy and chemoprevention against HCC especially in combination with other angiostatic agents.
血管生成是支持肝细胞癌（HCC）生长以及肝癌发生的一个复杂而关键的过程。最近的研究表明，肾素-血管紧张素系统（RAS）参与了包括 HCC 在内的多种癌症。一些研究已经证明，临床使用的血管紧张素转换酶抑制剂（ACE-I）抑制血管紧张素-II（AT-II）可显著减弱 HCC 的生长和肝癌发生，并下调一种强效的血管生成因子，即血管内皮生长因子（VEGF）。当与临床可用药物（如干扰素（IFN）和维生素 K（VK））联合使用时，ACE-I 比单一药物具有更强的抗肿瘤活性，除了抑制实验模型和临床实践中的肿瘤内血管生成。众所周知，AT-II 在胰岛素抵抗（IR）中发挥重要作用，IR 据报道与 HCC 的进展有关。在 IR 条件下，ACE-I 和支链氨基酸（BCAA）的组合对 HCC 具有明显的化学预防作用。除了 AT-II 之外，在 AT-II 下游发挥作用的醛固酮（Ald）也参与了 HCC 的发展，临床使用的选择性 Ald 阻滞剂（SAB）可显著抑制 HCC 的生长和肝癌发生。由于 ACE-I、IFN、VK、BCAA 和 SAB 已经在广泛的临床应用中，没有任何严重的不良反应，它们可能代表了针对 HCC 的癌症治疗和化学预防的一种潜在的新策略，特别是与其他血管生成抑制剂联合使用时。
