Role of COX-independent targets of NSAIDs and related compounds in cancer prevention and treatment.
Role of COX-independent targets of NSAIDs and related compounds in cancer prevention and treatment.
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DOI：
10.1159/000071377
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发表时间：
2003
期刊：
影响因子：
--
通讯作者：
J. Soh;I. Weinstein
中科院分区：
文献类型：
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作者：
J. Soh;I. Weinstein
非甾体类抗炎药（NSAIDs）已被证明在多种系统中具有抗肿瘤作用，包括人类癌细胞系的体外细胞培养、小鼠和大鼠的癌变模型、啮齿动物的肿瘤生长抑制试验和临床试验[综述，见1,2]。各种非甾体抗炎药对环氧化酶(COX)-1和/或COX-2酶活性的抑制作用以及COX-1和COX-2在肿瘤发生中的作用在本书的其他章节中进行了综述。然而，各种非甾体抗炎药对癌细胞发挥其抗增殖作用的确切机制尚不清楚。新出现的证据表明，至少在某些情况下，这些影响可以通过不依赖cox的机制发挥作用。在这一章中，我们综述了近年来在非甾体抗炎药及其相关化合物的新分子靶点鉴定方面的进展。希望阐明这些分子靶点和抑制细胞增殖和/或诱导细胞凋亡的下游信号通路将有助于开发更有效的癌症预防和治疗方法，同时最大限度地减少潜在的毒性。
BackgroundNonsteroidal anti-inflammatory drugs (NSAIDs) have been shown to have antitumor effects in various systems including in vitro cell cultures of human cancer cell lines, mouse and rat models of carcinogenesis, tumor growth inhibition assays in rodents and clinical trials [for reviews, see 1, 2]. The effects of various NSAIDs on inhibition of cyclooxygenase (COX)-1 and/or COX-2 enzymatic activity and the roles of COX-1 and COX-2 in tumorigenesis are reviewed in the other chapters of this book. However, the precise mechanisms by which various NSAIDs exert their antiproliferative effects on cancer cells are not known. Emerging evidence suggests that these effects can, at least in some cases, be exerted through COX-independent mechanisms. In this chapter, we review recent progress in the identification of novel molecular targets of NSAIDs and related compounds. Hopefully, elucidation of these molecular targets and the downstream signaling pathways that inhibit cell proliferation and/or induce apoptosis will facilitate the development of more effective approaches for cancer prevention and treatment, while minimizing potential toxicities.