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 proliferationand apoptosis in 1,2-dimethylhydrazine dihydrochloride (DMH) induced colon lesion development. Male SDrats were divided into four groups: Group 1 controls receiving the vehicle treatment; Group 2 administeredDMH weekly (30 mg/kg body weight, subcutaneously) alone; Group 3, DMH weekly plus etoricoxib (0.64 mg/kgbody weight, orally) daily; and Group 4, etoricoxib alone. After six weeks of treatment, animals were sacrificedand colons were analysed for morphological and histopathological features. Well characterized pre-neoplasticaberrations such as multiple plaque lesions, hyperplasia and dysplasia were found in the DMH treated groupwhereas these features were reduced with co-administration of etoricoxib. To study apoptosis, colonocyteswere isolated by metal chelation from colonic sacs and studied by fluorescent staining and further confirmedby DNA fragmentation. The DMH treated animals had fewer apoptotic nuclei as compared to the controls, butnumbers were higher with DMH+etoricoxib as well as etoricoxib alone. Expression of proliferative cell nuclearantigen (PCNA), assessed by Western blot analysis and immunohistochemistry, was found to be elevated byDMH 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-apoptoticand anti- proliferative agent in the colon.