Menter David G
Department of Clinical Cancer Prevention, The University of Texas M.D. Anderson Cancer Center, Box 236, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
Expert Opin Investig Drugs. 2002 Dec;11(12):1749-64. doi: 10.1517/13543784.11.12.1749.
Prostaglandin synthesis by a number of enzymes is important at all stages during the genesis of cancer. The availability of prostaglandin H(2) as a substrate for prostaglandin production is a critical control point in its synthesis. Cyclooxygenase (COX) occurs in two forms (COX-1 and -2) and acts as the rate-limiting enzyme that generates prostaglandin H(2). COX-1 is produced as a steady-state enzyme, while COX-2 is heavily involved in inflammation and tumorigenesis. Differences in the catalytic sites of these enzymes are utilised to generate COX-2 selective inhibitors. Certain chemical characteristics of non-steroidal anti-inflammatory drugs and COX-2 selective inhibitors make some of these inhibitors more effective against COX-2 than others. Epidemiological, animal and preclinical data demonstrate the promise of non-steroidal anti-inflammatory drugs and COX-2 selective inhibitors as anticancer agents. Ongoing clinical trials are designed to determine the efficacy of non-steroidal anti-inflammatory drugs and COX-2 selective inhibitors in the prevention and treatment of many types of cancer.
多种酶合成前列腺素在癌症发生的各个阶段都很重要。前列腺素H2作为前列腺素生成的底物，其可用性是其合成中的关键控制点。环氧化酶（COX）有两种形式（COX - 1和COX - 2），是生成前列腺素H2的限速酶。COX - 1作为一种稳态酶产生，而COX - 2则大量参与炎症和肿瘤发生。利用这些酶催化位点的差异来生成COX - 2选择性抑制剂。非甾体抗炎药和COX - 2选择性抑制剂的某些化学特性使其中一些抑制剂对COX - 2的作用比其他抑制剂更有效。流行病学、动物和临床前数据表明非甾体抗炎药和COX - 2选择性抑制剂作为抗癌药物具有前景。正在进行的临床试验旨在确定非甾体抗炎药和COX - 2选择性抑制剂在预防和治疗多种癌症方面的疗效。
