Ornelas Argentina, Zacharias-Millward Niki, Menter David G, Davis Jennifer S, Lichtenberger Lenard, Hawke David, Hawk Ernest, Vilar Eduardo, Bhattacharya Pratip, Millward Steven
Department of Cancer Systems Imaging, Division of Diagnostic Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Department of Gastrointestinal (GI) Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Cancer Metastasis Rev. 2017 Jun;36(2):289-303. doi: 10.1007/s10555-017-9675-z.
After more than a century, aspirin remains one of the most commonly used drugs in western medicine. Although mainly used for its anti-thrombotic, anti-pyretic, and analgesic properties, a multitude of clinical studies have provided convincing evidence that regular, low-dose aspirin use dramatically lowers the risk of cancer. These observations coincide with recent studies showing a functional relationship between platelets and tumors, suggesting that aspirin's chemopreventive properties may result, in part, from direct modulation of platelet biology and biochemistry. Here, we present a review of the biochemistry and pharmacology of aspirin with particular emphasis on its cyclooxygenase-dependent and cyclooxygenase-independent effects in platelets. We also correlate the results of proteomic-based studies of aspirin acetylation in eukaryotic cells with recent developments in platelet proteomics to identify non-cyclooxygenase targets of aspirin-mediated acetylation in platelets that may play a role in its chemopreventive mechanism.
一个多世纪以来，阿司匹林仍然是西医中最常用的药物之一。尽管主要因其抗血栓形成、解热和镇痛特性而被使用，但大量临床研究提供了令人信服的证据，表明定期服用低剂量阿司匹林可显著降低患癌风险。这些观察结果与最近显示血小板与肿瘤之间存在功能关系的研究相吻合，表明阿司匹林的化学预防特性可能部分源于对血小板生物学和生物化学的直接调节。在此，我们对阿司匹林的生物化学和药理学进行综述，特别强调其在血小板中依赖环氧化酶和不依赖环氧化酶的作用。我们还将基于蛋白质组学的阿司匹林在真核细胞中乙酰化研究结果与血小板蛋白质组学的最新进展相关联，以确定阿司匹林介导的血小板乙酰化的非环氧化酶靶点，这些靶点可能在其化学预防机制中发挥作用。
