Ino Kazuhiko, Shibata Kiyosumi, Kajiyama Hiroaki, Nawa Akihiro, Nomura Seiji, Kikkawa Fumitaka
Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
Expert Opin Biol Ther. 2006 Mar;6(3):243-55. doi: 10.1517/14712598.6.3.243.
Angiotensin II (Ang II), a main effector peptide in the renin-angiotensin system (RAS), plays a fundamental role as a vasoconstrictor in controlling cardiovascular function and renal homeostasis. Ang II also acts as a growth promoter or angiogenic factor via type 1 angiotensin II receptors (AT1Rs) in certain tumour cell lines. Recent studies have shown the activation of the local RAS in various tumour tissues, including the abundant generation of Ang II by angiotensin-converting enzyme (ACE) and the upregulation of AT1R expression. Thus, considerable attention has been paid to the role of the RAS in cancer and its blockade as a new approach to the treatment of cancer. There is increasing evidence that the Ang II-AT1R system is involved in tumour growth, angiogenesis and metastasis in experimental models, suggesting the therapeutic potential of an ACE inhibitor and AT1R blocker, both of which have been used as antihypertensive drugs. In addition, specific Ang II-degrading enzymes are expressed in tumours and play a regulatory role in cell proliferation and invasion. This review focuses on the role of the Ang II-AT1R system in solid tumours, particularly in the progression of gynaecological cancer, and presents the clinical potential of manipulating the angiotensin system as a novel and promising strategy for cancer treatment.
血管紧张素II(Ang II)是肾素-血管紧张素系统(RAS)中的一种主要效应肽,作为血管收缩剂在控制心血管功能和肾脏内环境稳定方面发挥着重要作用。在某些肿瘤细胞系中,Ang II还通过1型血管紧张素II受体(AT1Rs)作为生长促进剂或血管生成因子发挥作用。最近的研究表明,各种肿瘤组织中的局部RAS被激活,包括血管紧张素转换酶(ACE)大量生成Ang II以及AT1R表达上调。因此,RAS在癌症中的作用及其作为一种新的癌症治疗方法的阻断作用受到了相当大的关注。越来越多的证据表明,在实验模型中,Ang II-AT1R系统参与肿瘤生长、血管生成和转移,这表明ACE抑制剂和AT1R阻滞剂具有治疗潜力,这两种药物都已被用作抗高血压药物。此外,特定的Ang II降解酶在肿瘤中表达,并在细胞增殖和侵袭中发挥调节作用。本综述重点关注Ang II-AT1R系统在实体瘤中的作用,特别是在妇科癌症进展中的作用,并介绍了操纵血管紧张素系统作为一种新颖且有前景的癌症治疗策略的临床潜力。