Laboratory of Stem Cell Biology, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
Collaborative Innovation Center of Biotherapy, Chengdu, China.
Med Res Rev. 2019 Jan;39(1):114-145. doi: 10.1002/med.21514. Epub 2018 Jun 1.
The nonsteroidal anti-inflammatory agent aspirin is widely used for preventing and treating cardiovascular and cerebrovascular diseases. In addition, epidemiologic evidences reveal that aspirin may prevent a variety of human cancers, while data on the association between aspirin and some kinds of cancer are conflicting. Preclinical studies and clinical trials also reveal the therapeutic effect of aspirin on cancer. Although cyclooxygenase is a well-known target of aspirin, recent studies uncover other targets of aspirin and its metabolites, such as AMP-activated protein kinase, cyclin-dependent kinase, heparanase, and histone. Accumulating evidence demonstrate that aspirin may act in different cell types, such as epithelial cell, tumor cell, endothelial cell, platelet, and immune cell. Therefore, aspirin acts on diverse hallmarks of cancer, such as sustained tumor growth, metastasis, angiogenesis, inflammation, and immune evasion. In this review, we focus on recent progress in the use of aspirin for cancer chemoprevention and therapy, and integratively analyze the mechanisms underlying the anticancer effects of aspirin and its metabolites. We also discuss mechanisms of aspirin resistance and describe some derivatives of aspirin, which aim to overcome the adverse effects of aspirin.
非甾体类抗炎药阿司匹林被广泛用于预防和治疗心脑血管疾病。此外，流行病学证据表明，阿司匹林可能预防多种人类癌症，而阿司匹林与某些癌症之间的关联的数据存在矛盾。临床前研究和临床试验也揭示了阿司匹林对癌症的治疗作用。尽管环氧化酶是阿司匹林的一个众所周知的靶点，但最近的研究揭示了阿司匹林及其代谢物的其他靶点，如 AMP 激活的蛋白激酶、细胞周期蛋白依赖性激酶、乙酰肝素酶和组蛋白。越来越多的证据表明，阿司匹林可能在不同的细胞类型中发挥作用，如上皮细胞、肿瘤细胞、内皮细胞、血小板和免疫细胞。因此，阿司匹林作用于癌症的多种特征，如持续的肿瘤生长、转移、血管生成、炎症和免疫逃逸。在这篇综述中，我们重点关注阿司匹林在癌症化学预防和治疗中的最新应用进展，并综合分析阿司匹林及其代谢物抗癌作用的机制。我们还讨论了阿司匹林耐药的机制，并描述了一些旨在克服阿司匹林不良反应的阿司匹林衍生物。
