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靶向COX-2用于癌症治疗的最新进展:综述

Recent advances in targeting COX-2 for cancer therapy: a review.

作者信息

Kassab Asmaa E

机构信息

Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Cairo University Kasr El-Aini Street, P.O. Box 11562 Cairo Egypt

出版信息

RSC Med Chem. 2025 Apr 21. doi: 10.1039/d5md00196j.

Abstract

Cyclooxygenase-2 (COX-2) is involved in the production of prostaglandins and thromboxanes, which control biological processes like inflammation, angiogenesis, and cell division. Numerous premalignant tissues and many human malignant tumors overexpress COX-2. Metabolites from COX-2 may support tumor growth, transformation, invasion, metastatic dissemination, premalignant hyperproliferation, downregulation of apoptosis, and tumor survival. COX-2 also triggers activity like cancer stem cells (CSCs). Populations of CSCs isolated from many cancer types are linked to overexpression of COX-2. Using nonsteroidal anti-inflammatory drugs (NSAIDs) reduces the risk of solid tumors, including colon, stomach, and esophageal malignancies. The anticancer potential of NSAIDs is mediated COX-2 dependent or COX-2 independent pathways. For cancer patients, COX-2 may be a crucial target for therapeutic and chemoprotective measures. This review introduces the involvement of COX-2 in cancer different pathways and provides a comprehensive review of the most recent updates on COX-2 inhibitors as potential anticancer candidates. This review aims to spark fresh thinking in the pursuit of more logical COX-2 inhibitor designs that may effectively treat cancer.

摘要

环氧化酶-2(COX-2)参与前列腺素和血栓素的生成,而前列腺素和血栓素可控制炎症、血管生成和细胞分裂等生物学过程。许多癌前组织和多种人类恶性肿瘤均过度表达COX-2。COX-2的代谢产物可能支持肿瘤生长、转化、侵袭、转移扩散、癌前细胞过度增殖、细胞凋亡下调以及肿瘤存活。COX-2还会触发类似癌症干细胞(CSCs)的活性。从多种癌症类型中分离出的癌症干细胞群体与COX-2的过度表达有关。使用非甾体抗炎药(NSAIDs)可降低实体瘤的风险,包括结肠癌、胃癌和食管癌。NSAIDs的抗癌潜力是通过COX-2依赖性或COX-2非依赖性途径介导的。对于癌症患者而言,COX-2可能是治疗和化学预防措施的关键靶点。本综述介绍了COX-2在癌症不同途径中的作用,并全面回顾了COX-2抑制剂作为潜在抗癌候选药物的最新进展。本综述旨在激发新的思路,以寻求更合理的COX-2抑制剂设计,从而有效治疗癌症。

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