Department of Pharmacology, School of Medicine, University of Occupational and Environmental Health, Japan.
Department of Pharmacology, School of Medicine, University of Occupational and Environmental Health, Japan.
Biochem Pharmacol. 2018 May;151:96-103. doi: 10.1016/j.bcp.2018.03.008. Epub 2018 Mar 10.
Hypertension, which often exists as a comorbid condition in cancer patients, is considered as a factor affecting cancer progression. The renin-angiotensin system (RAS) plays an important role in the regulation of blood pressure, and angiotensin II (Ang II) is a well-known pressor peptide in RAS. There is also accumulated evidence indicating that Ang II plays a critical role in the metastasis of various cancers by modulating adhesion, migration invasion, proliferation, and angiogenesis. Consistent with this, large epidemiological studies have reported the potential beneficial effects of angiotensin-converting enzyme (ACE) inhibitors and Ang II type 1 receptor blockers (ARBs) against cancer metastasis; however, some of the results remain controversial. Although the precise Ang II-related mechanisms involved in cancer metastasis are not completely clear yet, a number of basic and meta-analytic studies have shown that ACE inhibitors and ARBs reduce the metastatic potential of tumors. In this review, we summarize the relationships among hypertension, RAS, and metastasis as demonstrated in basic and clinical studies. Finally, we discuss the possibility of using RAS inhibitors as anti-metastatic drugs.
高血压常作为癌症患者的合并症存在，被认为是影响癌症进展的一个因素。肾素-血管紧张素系统（RAS）在血压调节中发挥着重要作用，血管紧张素 II（Ang II）是 RAS 中一种众所周知的升压肽。有越来越多的证据表明，Ang II 通过调节黏附、迁移、侵袭、增殖和血管生成，在各种癌症的转移中发挥关键作用。与此一致的是，大型流行病学研究报告了血管紧张素转换酶（ACE）抑制剂和血管紧张素 II 型 1 受体阻滞剂（ARB）对癌症转移的潜在有益作用；然而，一些结果仍存在争议。尽管 ACE 抑制剂和 ARB 降低肿瘤转移潜力的具体 Ang II 相关机制尚不完全清楚，但一些基础和荟萃分析研究表明，ACE 抑制剂和 ARB 减少了肿瘤的转移潜能。在这篇综述中，我们总结了基础和临床研究中表明的高血压、RAS 与转移之间的关系。最后，我们讨论了将 RAS 抑制剂作为抗转移药物的可能性。
