College of Pharmacy, Guangxi Medical University, Nanning, 530021, Guangxi, PR China.
College of Pharmacy, Guangxi Medical University, Nanning, 530021, Guangxi, PR China.
Eur J Pharmacol. 2021 May 5;898:173989. doi: 10.1016/j.ejphar.2021.173989. Epub 2021 Feb 28.
Aspirin is an old drug extracted from willow bark and is widely used for the prevention and treatment of cardiovascular diseases. Accumulating evidence has shown that aspirin use may significantly reduce the angiogenesis of cancer; however, the mechanism of the association between angiogenesis and aspirin is complex. Although COX-1 is widely known as a target of aspirin, several studies reveal other antiangiogenic targets of aspirin, such as angiotensin II, glucose transporter 1, heparanase, and matrix metalloproteinase. In addition, some data indicates that aspirin may produce antiangiogenic effects after acting in different cell types, such as endothelial cells, platelets, pericytes, and macrophages. In this review, we concentrate on research regarding the antiangiogenic effects of aspirin in cancer, and we discuss the molecular mechanisms of aspirin and its metabolites. Moreover, we discuss some mechanisms through which aspirin treatment may normalize existing blood vessels, including preventing the disintegration of endothelial adheres junctions and the recruitment of pericytes. We also address the antiangiogenic effects and the underlying mechanisms of aspirin derivatives, which are aimed at improving safety and efficacy.
阿司匹林是从柳树皮中提取的一种古老药物，广泛用于预防和治疗心血管疾病。越来越多的证据表明，阿司匹林的使用可能会显著抑制肿瘤的血管生成；然而，血管生成与阿司匹林之间的关联机制非常复杂。尽管 COX-1 被广泛认为是阿司匹林的靶点，但有几项研究揭示了阿司匹林的其他抗血管生成靶点，如血管紧张素 II、葡萄糖转运蛋白 1、乙酰肝素酶和基质金属蛋白酶。此外，一些数据表明，阿司匹林可能在作用于不同的细胞类型（如内皮细胞、血小板、周细胞和巨噬细胞）后产生抗血管生成作用。在这篇综述中，我们集中研究阿司匹林在癌症中的抗血管生成作用，并讨论阿司匹林及其代谢物的分子机制。此外，我们还讨论了阿司匹林治疗可能使现有血管正常化的一些机制，包括防止内皮细胞黏附连接的解体和周细胞的募集。我们还探讨了旨在提高安全性和疗效的阿司匹林衍生物的抗血管生成作用及其潜在机制。
