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Role of cyclooxygenase-2 in colorectal cancer

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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.

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  1. Mayo Clinic, Division of Gastroenterology and Hepatology, Division of Medical Oncology, 200 First Street SW, Rochester, MN, 55905

    Frank A. Sinicrope & Sharlene Gill

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Sinicrope, F.A., Gill, S. Role of cyclooxygenase-2 in colorectal cancer. Cancer Metastasis Rev 23, 63–75 (2004). https://doi.org/10.1023/A:1025863029529

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