Nimesulide and melatonin in mammary carcinogenesis prevention in female Sprague-Dawley rats

Tumorsuppressive effects of a selective inhibitor of cyclooxygenase-2 (COX-2) nimesulide (NIM) activity and pineal hormone melatonin (MEL) and their combination in two chemopreventive studies of mammary carcinogenesis were evaluated. Mamary tumors in female Sprague-Dawley rats were induced by N-methyl-N-nitrosourea (NMU) and by 7,12-dimethylbenz(a)anthracene (DMBA), respectively. The treatment with NIM (applied subcutaneously twice a week in the dose of 5 mg/kg b.w.) and MEL (given daily diluted in drinking water in concentration 20microg/ml) began several days before carcinogen administration and lasted until the end of the experiment. The tumor incidence, frequency, latency period and tumor volume as parameters of mammary carcinogenesis were evaluated. Moreover, the effect of chemopreventives on body weight, food and water intake were recorded. Changes of selected parameters of lipid and carbohydrate metabolism in the serum and chosen organs were evaluated in the NMU experiment. In the NIM-treated group in the NMU experiment, the tumor incidence decreased by 34.5% (p < 0.05), tumor frequency per group by 40% (p < 0.05) and tumor volume gain by 39% when compared to the control group. Tumorsuppressive effect of MEL was not observed. In DMBA-induced carcinogenesis an oncostatic effect of NIM was not observed; MEL administration decreased tumor incidence by 21.5% (p < 0.05), tumor frequency per group by 22.5% and tumor volume gain by 43.5%. Combined chemoprevention of NIM+MEL was very similar to that of chemopreventives administered alone. MEL lowered food and water intake and body weight gain in DMBA-induced carcinogenesis. It increased glycogen and cholesterol content in the liver, triacyglycerol and phospholipid concentrations in the bone marrow and decreased malondialdehyde concentration at the same tissue of tumor-bearing animals. NIM did not significantly influence the selected metabolic parameters, excepting the decrease in serum glucose concentration in tumor-bearing rats.