The role of COX-2 in intestinal inflammation and colorectal cancer.
The role of COX-2 in intestinal inflammation and colorectal cancer.
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DOI：
10.1038/onc.2009.421
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发表时间：
2010-02-11
期刊：
影响因子：
8
通讯作者：
DuBois, R. N.
中科院分区：
文献类型：
--
作者：
Wang, D.;DuBois, R. N.
结直肠癌（CRC）是一种异质性疾病，包括至少三种主要形式：遗传性、散发性和结肠炎相关性CRC。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CRC的危险因素。由于环氧化酶-2（考克斯-2）的高表达存在于大多数结直肠癌组织中，并与结直肠癌患者的生存率降低相关，因此研究人员试图评估非甾体抗炎药（NSAID）和选择性考克斯-2抑制剂（COXIB）对结直肠癌预防和治疗的影响。流行病学研究、临床试验和动物实验表明，非甾体抗炎药是最有前途的化学预防药物之一。NSAID主要通过抑制考克斯-2活性减少前列腺素产生来发挥其抗炎和抗肿瘤作用。在这篇综述中，我们强调突破我们的理解考克斯-2在CRC和炎症性肠病（IBD）的作用。这些最新数据为重新评价考克斯-2作为多种恶性肿瘤的预后和预测标志物以及重新评价考克斯-2抑制剂在适当选择的癌症预防和治疗患者中的相对获益和风险提供了理论基础。
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. Since elevated cyclooxygenase-2 (COX-2) expression was found in most colorectal cancer 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 prevention and treatment. The epidemiologic 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 anti-tumor effects primarily by reducing prostaglandin production via 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 (IBD). 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 COX-2 inhibitors in appropriately selected patients for cancer prevention and treatment.
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