Department of Molecular, Cellular and Biomedical Sciences, Sophie Davis School of Biomedical Education, City University of New York School of Medicine, New York, NY 10031, USA.
Graduate Program in Biology, City University of New York Graduate Center, New York, NY 10091, USA.
Int J Mol Sci. 2022 Jan 27;23(3):1432. doi: 10.3390/ijms23031432.
Acute inflammation or resolved inflammation is an adaptive host defense mechanism and is self-limiting, which returns the body to a state of homeostasis. However, unresolved, uncontrolled, or chronic inflammation may lead to various maladies, including cancer. Important evidence that links inflammation and cancer is that nonsteroidal anti-inflammatory drugs (NSAIDs), such as aspirin, reduce the risk and mortality from many cancers. The fact that NSAIDs inhibit the eicosanoid pathway prompted mechanistic drug developmental work focusing on cyclooxygenase (COX) and its products. The increased prostaglandin E2 levels and the overexpression of COX-2 in the colon and many other cancers provided the rationale for clinical trials with COX-2 inhibitors for cancer prevention or treatment. However, NSAIDs do not require the presence of COX-2 to prevent cancer. In this review, we highlight the effects of NSAIDs and selective COX-2 inhibitors (COXIBs) on targets beyond COX-2 that have shown to be important against many cancers. Finally, we hone in on specialized pro-resolving mediators (SPMs) that are biosynthesized locally and, in a time, -dependent manner to promote the resolution of inflammation and subsequent tissue healing. Different classes of SPMs are reviewed, highlighting aspirin's potential in triggering the production of these resolution-promoting mediators (resolvins, lipoxins, protectins, and maresins), which show promise in inhibiting cancer growth and metastasis.
急性炎症或已解决的炎症是一种适应性宿主防御机制，具有自限性，可使机体恢复到稳态。然而，未解决的、不受控制的或慢性炎症可能导致各种疾病，包括癌症。有重要证据表明炎症与癌症之间存在关联，即非甾体抗炎药（NSAIDs），如阿司匹林，可降低多种癌症的风险和死亡率。事实上，NSAIDs 抑制类二十烷酸途径，这促使人们针对环氧化酶（COX）及其产物开展了机制性药物研发工作。COX-2 在结肠和许多其他癌症中的前列腺素 E2 水平升高和过度表达，为 COX-2 抑制剂用于癌症预防或治疗提供了依据。然而，NSAIDs 并不需要 COX-2 的存在来预防癌症。在这篇综述中，我们强调了 NSAIDs 和选择性 COX-2 抑制剂（COXIBs）对 COX-2 以外靶点的作用，这些靶点在对抗多种癌症方面显示出重要作用。最后，我们关注了局部生物合成的特殊促解决介质（SPMs），它们以时间依赖的方式促进炎症的解决和随后的组织愈合。综述了不同类别的 SPMs，强调了阿司匹林在触发这些促解决介质（消退素、脂氧素、保护素和maresins）产生方面的潜力，这些介质在抑制癌症生长和转移方面显示出希望。
