Prevention of colorectal cancer using COX-2 inhibitors: Basic science and clinical applications

被引:27
作者
Chu, AJ
Chou, TH
Chen, BD
机构
[1] Wayne State Univ, Sch Med, Dept Internal Med, Detroit, MI 48201 USA
[2] Shantou Univ, Multidisciplinary Res Ctr, Shantou, Peoples R China
[3] Univ Texas, MD Anderson Canc Ctr, Dept GI Med Oncol, Houston, TX 77030 USA
来源
FRONTIERS IN BIOSCIENCE-LANDMARK | 2004年 / 9卷
关键词
COX-2; inhibitor; colorectal cancer; cancer prevention; NSAID; prostaglandin; review;
D O I
10.2741/1429
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Cyclooxygenase-2 (COX-2), an inducible prostaglandin G/H synthase, is overexpressed in preneoplastic tissues and several human cancers including colorectal cancer. Evidence linking COX-2 activity to carcinogenesis was derived from epidemiologic studies and animal models with defect adenomatous polyposis coli (APC) gene. PGE(2) induced by COX-2 exerts several biological properties that may be advantageous for tumorigenesis: 1) Promoting angiogenesis ( increased VEGF, bFGF, and PDGF production), 2) Anti-apoptosis mechanism ( via increased bcl-2 and Akt activity), 3) Stimulating tumor metastasis ( by increasing matrix metalloproteinases) and 4) Decreased immune surveillance ( decreased cytokine production and NK activity). In addition, COX-2 reaction can cause DNA oxidation and induce mutations. Chemoprevention of colorectal cancer has attracted great attention in recent years. Epidemiologic data showed that chronic intake of traditional nonsteroidal anti-inflammatory drugs ( NSAIDs) could reduce the incidence of colorectal cancer. Recent clinical trial studies showed that celecoxib, a selective COX-2 inhibitor, is equally effective in reducing colorectal adenomas in animal models and patients with familial adenomatous polyposis FAP), yet with superior GI safety. Two COX-2 inhibitors ( celecoxib and refocoxib) have been approved by FDA as adjuncts to usual care in FPA patients, and are currently being studied in patients with sporadic adenomas and other types of cancers. These studies are expected to generate evidence in favor of targeting COX-2 and its gene products as chemopreventive strategies, which may provide an alternative in current approach to reducing the morbidity and mortality of this disease.
引用
收藏
页码:2697 / 2713
页数:17
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