Abstract
Cyclooxygenase-2 (COX-2) is an inducible enzyme that regulates prostaglandin synthesis and is overexpressed at sites of inflammation and in several epithelial cancers. Recently, a causal link for COX-2 in epithelial tumorigenesis was shown in genetically-manipulated animal models of colon and breast carcinoma. Data indicate that COX-2 is involved in the regulation of apoptosis, angiogenesis, and tumor cell invasiveness, which appear to contribute to its effects on tumorigenesis. Multiple studies have shown that nonselective COX and selective COX-2 inhibitors effectively prevent experimental colon cancer. Furthermore, sulindac and the selective COX-2 inhibitor celecoxib were shown to regress colorectal polyps in patients with familial adenomatous polyposis. Although the exact anti-tumor mechanisms of these agents await further study, data indicate that both COX-dependent and COX-independent mechanisms may be important. In this review, the association between COX-2 and colorectal tumorigenesis and potential mechanisms of this effect are discussed. Additionally, evidence supporting the role of NSAIDs and selective COX-2 inhibitors for the prevention and treatment of human colorectal cancer is reviewed.
Original language | English (US) |
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Pages (from-to) | 63-75 |
Number of pages | 13 |
Journal | Cancer and Metastasis Reviews |
Volume | 23 |
Issue number | 1-2 |
DOIs | |
State | Published - Jan 2004 |
Keywords
- Colorectal cancer
- Coxibs
- Cyclooxygenase-2
- NSAIDs
- Tumorigenesis
ASJC Scopus subject areas
- Oncology
- Cancer Research