Taketo M M
Laboratory of Biomedical Genetics, Graduate School of Pharmaceutical Sciences, University of Tokyo, Bunkyo, Japan.
J Natl Cancer Inst. 1998 Nov 4;90(21):1609-20. doi: 10.1093/jnci/90.21.1609.
The rate-limiting step in arachidonate metabolism is mediated by enzymes known as cyclooxygenases (COXs). These enzymes catalyze the biosynthesis of prostaglandin H2, the precursor of molecules such as prostaglandins, prostacyclin, and thromboxanes. The COX enzyme family consists of the classical COX-1 enzyme, which is constitutively expressed in many tissues, and a second isozyme, i.e., COX-2, which is induced by various stimuli, such as mitogens and cytokines, and is involved in many inflammatory reactions. Because nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit both COX-1 and COX-2, these drugs also cause unwanted side effects, exemplified by gastrointestinal bleeding. Accumulating evidence indicates that NSAIDs can reduce the incidence of colorectal cancers in human and experimental animals and can reduce the number and size of polyps in patients with familial adenomatous polyposis. This Part II (of a two-part review) focuses on the growing clinical and experimental evidence that NSAIDS and COX-2 inhibitors can influence the risk of colon (and possibly of other) cancers.
花生四烯酸代谢的限速步骤由称为环氧化酶（COXs）的酶介导。这些酶催化前列腺素H2的生物合成，前列腺素H2是前列腺素、前列环素和血栓素等分子的前体。COX酶家族由在许多组织中组成性表达的经典COX-1酶和第二种同工酶即COX-2组成，COX-2由各种刺激物如丝裂原和细胞因子诱导，并参与许多炎症反应。由于非甾体抗炎药（NSAIDs）同时抑制COX-1和COX-2，这些药物也会引起不良副作用，如胃肠道出血。越来越多的证据表明，NSAIDs可以降低人类和实验动物患结直肠癌的发生率，并可以减少家族性腺瘤性息肉病患者息肉的数量和大小。本（两部分综述的）第二部分重点关注越来越多的临床和实验证据，即NSAIDs和COX-2抑制剂可以影响结肠癌（以及可能其他癌症）的风险。
