Telliez Aurélie, Furman Christophe, Pommery Nicole, Hénichart Jean-Pierre
Institut de Chimie Pharmaceutique Albert Lespagnol, EA 2692, 3 rue du Professeur Laguesse, BP 83, F-59006 Lille, France.
Anticancer Agents Med Chem. 2006 May;6(3):187-208. doi: 10.2174/187152006776930891.
The biological role of COX-2, the inducible form of cyclooxygenase, is to convert arachidonic acid into prostaglandins (PGs) and thromboxanes (TXs). Overexpressed in many tumors, COX-2 plays a crucial role in cancer through synthesis of PGs which stimulate PGs receptors with subsequent enhancement of cellular proliferation, promotion of angiogenesis, inhibition of apoptosis, stimulation of invasion/motility, and suppression of immune responses. Depending on the tissue specificity and the cell type, several signaling pathways (Kinases, Rho, cGMP and Wnt), and transcription factors such as AP1, NFAT or NF-kappaB, are involved in COX-2 expression. In this review, we will describe mechanisms required by COX-2 metabolites to promote cancer development, and also the signaling pathways leading to COX-2 expression. In order to counteract the negative effects of COX-2 in cancerogenesis, chemicals interfering with COX-2 activity and expression were designed. We will give in the last part of this article, an overview of these potent chemicals interfering with the COX-2 signaling pathways involved in its expression or with its activity.
环氧化酶的诱导型COX-2的生物学作用是将花生四烯酸转化为前列腺素（PGs）和血栓素（TXs）。COX-2在许多肿瘤中过度表达，通过合成PGs在癌症中发挥关键作用，PGs刺激PGs受体，随后增强细胞增殖、促进血管生成、抑制细胞凋亡、刺激侵袭/迁移以及抑制免疫反应。根据组织特异性和细胞类型，多种信号通路（激酶、Rho、cGMP和Wnt）以及转录因子如AP1、NFAT或NF-κB参与COX-2的表达。在本综述中，我们将描述COX-2代谢产物促进癌症发展所需的机制，以及导致COX-2表达的信号通路。为了抵消COX-2在癌症发生中的负面影响，设计了干扰COX-2活性和表达的化学物质。我们将在本文的最后部分概述这些有效化学物质，它们干扰参与COX-2表达的信号通路或其活性。
