Matsuyama Masahide, Yoshimura Rikio
Department of Urology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka, 545-8585, Japan.
Subst Abuse. 2009 Dec 9;3:99-107. doi: 10.4137/sart.s2151.
Recent epidemiological studies and animal experiments have demonstrated that nonsteroidal anti-inflammatory drugs (NSAIDs) reduce the incidence of colorectal carcinoma. Cyclooxygenase (COX) is the principal target of NSAIDs. COX is the first oxidase in the process of prostaglandin production from arachidonic acid. COX enzyme may be involved in the initiation and/or the promotion of tumorigenesis due to NSAIDs inhibition of COX. Lipoxygenase (LOX) is also an initial enzyme in the pathway for producing leukotrienes from arachidonic acid. Similar to COX, LOX enzyme may also be involved in the initiation and/or promotion of tumorigenesis. Peroxisome proliferator activator-receptor (PPAR)-γ is a ligand-activated transcriptional factor belonging to the steroid receptor superfamily. PPAR-γ plays a role in both adipocyte differentiation and tumorigenesis. PPAR-γ is one target for cell growth modulation of NSAIDs. In this review, we report the expression of COX-2, LOX and PPAR-γ in human bladder tumor tissues as well as the effects of COX-2 and LOX inhibitors and PPAR-γ ligand.
近期的流行病学研究和动物实验表明,非甾体抗炎药(NSAIDs)可降低结直肠癌的发病率。环氧化酶(COX)是非甾体抗炎药的主要作用靶点。COX是花生四烯酸生成前列腺素过程中的首个氧化酶。由于非甾体抗炎药对COX的抑制作用,COX酶可能参与肿瘤发生的起始和/或促进过程。脂氧合酶(LOX)也是花生四烯酸生成白三烯途径中的起始酶。与COX类似,LOX酶也可能参与肿瘤发生的起始和/或促进过程。过氧化物酶体增殖物激活受体(PPAR)-γ是一种属于类固醇受体超家族的配体激活转录因子。PPAR-γ在脂肪细胞分化和肿瘤发生中均发挥作用。PPAR-γ是非甾体抗炎药调节细胞生长的一个靶点。在本综述中,我们报道了COX-2、LOX和PPAR-γ在人膀胱肿瘤组织中的表达情况,以及COX-2和LOX抑制剂及PPAR-γ配体的作用。