School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong, China.
Curr Cancer Drug Targets. 2011 May;11(4):412-20. doi: 10.2174/156800911795538110.
Angiotensin II (Ang II), a main effector peptide of the renin-angiotensin system (RAS), mediates a hormonal action in the maintenance of blood pressure and electrolyte levels, and thus fluid homeostasis. Ang II also mediates paracrine, autocrine and/or intracrine actions in the control of various specific functions of diverse tissue organs. In the pancreas, Ang II exerts a growth promoting, angiogenic influence via the mediation of angiotensin II type 1 receptor (AT1R). Recent studies have implicated inappropriate activation of the local RAS in pancreatic cancer, including upregulation of AT1R and the angiotensin-converting enzyme (ACE), which consequently enhance Ang II-induced tumour activity. In addition to acting in a classical antihypertensive capacity, RAS blockers (AT1R blockers or ACE inhibitors) may yield protective effects against pancreatic cancer, a highly aggressive malignancy that is intrinsically resistant to radiotherapy and chemotherapy. Substantial experimental data from studies using cell and animal models of pancreatic cancer support the notion that RAS regulates tumour growth, angiogenesis, and metastasis; and a convergence of such findings suggests that pharmacological RAS blockade could have therapeutic potential in the management of pancreatic cancer. This review critically appraises the current research progress on the role of RAS in pancreatic cancer, and discusses the potential for developing drugs that target RAS for treatment of pancreatic cancer.
血管紧张素 II（Ang II）是肾素-血管紧张素系统（RAS）的主要效应肽，在维持血压和电解质水平以及体液平衡方面发挥激素作用。Ang II 还通过血管紧张素 II 型 1 受体（AT1R）介导旁分泌、自分泌和/或胞内作用，控制各种组织器官的特定功能。在胰腺中，Ang II 通过血管紧张素 II 型 1 受体（AT1R）的介导发挥促生长、血管生成作用。最近的研究表明，局部 RAS 的异常激活与胰腺癌有关，包括 AT1R 和血管紧张素转换酶（ACE）的上调，这反过来增强了 Ang II 诱导的肿瘤活性。除了具有经典的降压作用外，RAS 阻滞剂（AT1R 阻滞剂或 ACE 抑制剂）可能对胰腺癌具有保护作用，胰腺癌是一种高度侵袭性的恶性肿瘤，对放疗和化疗具有内在抗性。来自胰腺癌细胞和动物模型研究的大量实验数据支持这样一种观点，即 RAS 调节肿瘤生长、血管生成和转移；这些发现的汇聚表明，药理学 RAS 阻断可能在胰腺癌的治疗中具有治疗潜力。本文批判性地评价了 RAS 在胰腺癌中的作用的研究进展，并讨论了针对 RAS 开发治疗胰腺癌药物的潜力。
