Role of cyclooxygenase-2 in the development and treatment of oesophageal adenocarcinoma.

Abstract

Background: Various studies suggest that aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) are promising anticancer agents. Epidemiological studies have found that long-term use of NSAIDs is associated with a reduced incidence of colorectal, gastric and oesophageal cancers, while experimental and clinical studies have demonstrated that treatment with NSAIDs causes a statistically significant reduction in both the number and the size of polyps in familial adenomatous polyposis (FAP) patients.

Methods: In this review, the mechanisms by which NSAIDs exert their chemopreventive and antineoplastic effects are described.

Results: Although the precise anticancer actions of NSAIDs are not fully explained, they probably involve inhibition of cyclooxygenase (COX), which is the rate-limiting enzyme in the conversion of arachidonic acid to prostaglandins. Two isoforms of this enzyme (COX-1 and COX-2) have been identified. COX-1 is constitutively expressed and considered to be a housekeeping gene, while COX-2 is not usually detectable in normal tissues, but can be readily induced in processes like inflammation, reproduction and carcinogenesis. The mechanisms by which COX-2 is thought to be involved in the carcinogenesis include resisting apoptosis, increasing cell proliferation, stimulating angiogenesis and modulating the invasive properties of cancer cells.

Conclusion: This report reviews the mechanisms by which COX-2 can contribute to carcinogenesis, its role in prognosis, and the possible place of selective COX-2 inhibitors in the prevention and treatment of gastrointestinal malignancies, focusing particularly on oesophageal cancer.