Celecoxib COX-2 inhibitor reduces APC gen mutagenesis in a murine experi-mental model of colonic carcinoma

Resumen

The role of celecoxib, a COX-2 inhibitor, in oncogenesis in colonic carcinoma is analysed inthe present study. Among the hypothesis advanced on molecular mechanisms ofoncogenesis we tried to test whether COX-2 would play dose of the mutagenic agentazoxymethane (15 mg/Kg.), Seventy-eight Wistar rats were divided into three groups of26 animals each. Group I (control) was untreated and maintained on a standard dietGroup II and III were treated with azoxymethane, Group III received additionally celecoxib0.9 mg/Kg/day. The experiment was terminated after 1 year of treatment and colonicbiopsies were obtained from all the animals. Overall death rate for groups II and III wasnear 50%. Four animals in group III did not developed carcinoma no adenomatous lesions.All the animals in group II showed histological changes compatible with carcinoma noadenomatous lesions. Difference was significant between both groups according to the Chi-square test (alfa 0.05). Previous works have shown that COX-2 inhibition disminishesmutagenesis in genes associated with colonic oncogenesis. The parallelism betweenmolecular changes of the APC-gen deletion and the histological found suggests that COX-2may be a promutagenic factor of this gen in this experimental model. The use of a COX-2inhibitor before the onset of preneoplastic lesions might prevent the appearance of the disease.