COX-2 inhibitors in cancer treatment and prevention, a recent development.
COX-2 inhibitors in cancer treatment and prevention, a recent development.
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DOI：
10.1097/00001813-200202000-00003
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发表时间：
2002-02
影响因子：
2.3
通讯作者：
Xìao-chun Xu
中科院分区：
文献类型：
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作者：
Xìao-chun Xu
流行病学和实验研究已经证明了非甾体抗炎药（NSAID）在预防人类癌症中的作用。NSAID通过抑制环氧合酶（考克斯）酶活性阻断内源性前列腺素合成。考克斯-2是花生四烯酸转化为异黄酮的关键同工酶，可被各种试剂如生长因子和肿瘤促进剂诱导，并且经常在各种肿瘤中过表达。考克斯-2对肿瘤细胞的致癌作用和恶性表型的贡献被认为与其以下能力有关：（i）增加胡萝卜素的产生，（ii）将原致癌物转化为致癌物，（iii）抑制细胞凋亡，（iv）促进血管生成，（v）调节炎症和免疫功能，和（vi）增加肿瘤细胞侵袭性，尽管一些研究表明NSAID具有考克斯-2非依赖性作用。许多使用考克斯-2抑制剂的临床试验正在进行中，这些研究的结果将增加我们对考克斯-2抑制在癌症治疗和预防中的理解。考克斯-2抑制剂与放疗或其他抗癌或防癌药物的联合应用可能会在未来的癌症预防和治疗中减少其副作用。最新进展的治疗和预防结肠癌，食管癌，肺癌，膀胱癌，乳腺癌和前列腺癌的非甾体抗炎药，特别是考克斯-2抑制剂，也进行了讨论。
Epidemiological and experimental studies have demonstrated the effect of non-steroidal anti-inflammatory drugs (NSAIDs) in the prevention of human cancers. NSAIDs block endogenous prostaglandin synthesis through inhibition of cyclooxygenase (COX) enzymatic activity. COX-2, a key isoenzyme in conversion of arachidonic acid to prostaglandins, is inducible by various agents such as growth factors and tumor promoters, and is frequently overexpressed in various tumors. The contribution of COX-2 to carcinogenesis and the malignant phenotype of tumor cells has been thought to be related to its abilities to (i) increase production of prostaglandins, (ii) convert procarcinogens to carcinogens, (iii) inhibit apoptosis, (iv) promote angiogenesis, (v) modulate inflammation and immune function, and (vi) increase tumor cell invasiveness, although some studies indicated that NSAIDs have COX-2-independent effects. A number of clinical trials using COX-2 inhibitors are in progress, and the results from these studies will increase our understanding of COX-2 inhibition in both cancer treatment and prevention. The combination of COX-2 inhibitors with radiation or other anti-cancer or cancer prevention drugs may reduce their side effects in future cancer prevention and treatment. Recent progress in the treatment and prevention of cancers of the colon, esophagus, lung, bladder, breast and prostate with NSAIDs, especially COX-2 inhibitors, is also discussed.