Colon cancer is common worldwide and accounts for significant morbidity and mortality in patients. Fortunately, epidemiological studies have demonstrated that continuous therapy with NSAIDs offers real promise of chemoprevention and adjunct therapy for colon cancer patients. Tumour growth is the result of complex regulation that determines the balance between cell proliferation and cell death. How NSAIDs affect this balance is important for understanding and improving treatment strategies and drug effectiveness. NSAIDs inhibit proliferation and impair the growth of colon cancer cell lines when tested in culture in vitro and many NSAIDs also prevent tumorigenesis and reduce tumour growth in animal models and in patients, but the relationship to inhibition of tumour cell proliferation is less convincing, principally due to gaps in the available data. High concentrations of NSAIDs are required in vitro to achieve cancer cell inhibition and growth retardation at varying time-points following treatment. However, the results from studies with colon cancer cell xenografts are promising and, together with better comparative data on anti-proliferative NSAID concentrations and doses (for in vitro and in vivo administration), could provide more information to improve our understanding of the relationships between these agents, dose and dosing regimen, and cellular environment.
The role of peroxisome proliferator‐activated receptor beta/delta (PPARβ/d) is not known but is believed to involve modulation of inflammation and mediation of differentiation in high‐turnover cell populations such as the intestinal epithelium. Cyclooxygenase (COX) inhibitors are anti‐inflammatory agents that affect proliferation in intestinal epithelial cells. This study examined the effect of COX‐inhibitor treatment on PPARβ/d expression and differentiation by immunohistochemical methods following treatment with the selective COX inhibitor nimesulide and found that PPARβ/δ expression is induced in the cytoplasm in crypt cells after 24 hours of treatment, the typical pattern of expression that was observed in untreated differentiated villous cells but not in untreated crypt cells. In addition, the differentiation marker Dolichos biflorus agglutinin (DBA) was expressed in greater parts of nimesulide‐treated crypt compared to the basal expression typically seen in untreated crypts indicating that nimesulide induces differentiation in crypt cells in the small intestine. Supported by the UCD School of Medicine/SSRA Research Scheme.
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