Anti-proliferative and apoptotic effects of etoricoxib, a selective COX-2 inhibitor, on 1,2-dimethylhydrazine dihydrochloride-induced colon carcinogenesis.

In the present study, we assessed effects of etoricoxib, a non-steroidal anti-inflammatory drug, on proliferation and apoptosis in 1,2-dimethylhydrazine dihydrochloride (DMH) induced colon lesion development. Male SD rats were divided into four groups: Group 1 controls receiving the vehicle treatment; Group 2 administered DMH weekly (30 mg/kg body weight, subcutaneously) alone; Group 3, DMH weekly plus etoricoxib (0.64 mg/kg body weight, orally) daily; and Group 4, etoricoxib alone. After six weeks of treatment, animals were sacrificed and colons were analysed for morphological and histopathological features. Well characterized pre-neoplastic aberrations such as multiple plaque lesions, hyperplasia and dysplasia were found in the DMH treated group whereas these features were reduced with co-administration of etoricoxib. To study apoptosis, colonocytes were isolated by metal chelation from colonic sacs and studied by fluorescent staining and further confirmed by DNA fragmentation. The DMH treated animals had fewer apoptotic nuclei as compared to the controls, but numbers were higher with DMH+etoricoxib as well as etoricoxib alone. Expression of proliferative cell nuclear antigen (PCNA), assessed by Western blot analysis and immunohistochemistry, was found to be elevated by DMH treatment group and again reduced by etoricoxib. Results for bromodeoxyuridine incorporation (BrdU) were in agreement. It may be concluded that the drug, etoricoxib, has the potential to act as an anti-apoptotic and anti- proliferative agent in the colon.