Wang D, Dubois R N
Department of Cancer Biology and GI Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030-4009, USA.
Oncogene. 2010 Feb 11;29(6):781-8. doi: 10.1038/onc.2009.421. Epub 2009 Nov 30.
Colorectal cancer (CRC) is a heterogeneous disease, including at least three major forms: hereditary, sporadic and colitis-associated CRC. A large body of evidence indicates that genetic mutations, epigenetic changes, chronic inflammation, diet and lifestyle are the risk factors for CRC. As elevated cyclooxygenase-2 (COX-2) expression was found in most CRC tissue and is associated with worse survival among CRC patients, investigators have sought to evaluate the effects of nonsteroidal anti-inflammatory drugs (NSAIDs) and selective COX-2 inhibitors (COXIBs) on CRC. The epidemiological studies, clinical trials and animal experiments indicate that NSAIDs are among the most promising chemopreventive agents for this disease. NSAIDs exert their anti-inflammatory and antitumor effects primarily by reducing prostaglandin production by inhibition of COX-2 activity. In this review, we highlight breakthroughs in our understanding of the roles of COX-2 in CRC and inflammatory bowel disease. These recent data provide a rationale for re-evaluating COX-2 as both the prognostic and the predictive marker in a wide variety of malignancies and for renewing the interest in evaluating relative benefits and risk of COXIBs in appropriately selected patients for cancer prevention and treatment.
结直肠癌（CRC）是一种异质性疾病，至少包括三种主要类型：遗传性、散发性和结肠炎相关性结直肠癌。大量证据表明，基因突变、表观遗传变化、慢性炎症、饮食和生活方式是结直肠癌的危险因素。由于在大多数结直肠癌组织中发现环氧化酶-2（COX-2）表达升高，且与结直肠癌患者较差的生存率相关，研究人员试图评估非甾体抗炎药（NSAIDs）和选择性COX-2抑制剂（COXIBs）对结直肠癌的影响。流行病学研究、临床试验和动物实验表明，NSAIDs是该疾病最有前景的化学预防药物之一。NSAIDs主要通过抑制COX-2活性减少前列腺素生成来发挥其抗炎和抗肿瘤作用。在本综述中，我们重点介绍了在理解COX-2在结直肠癌和炎症性肠病中的作用方面取得的突破。这些最新数据为重新评估COX-2作为多种恶性肿瘤的预后和预测标志物以及重新激发评估COXIBs在适当选择的癌症预防和治疗患者中的相对益处和风险的兴趣提供了理论依据。
