Rosiglitazone Shows Partial Oncostatic Effect in Rat Mammary Carcinogenesis

Abstract

Peroral antidiabetics from thiazolidinedione (glitazone) group showed oncostatic effects in preclinical models. This study evaluated chemopreventive effects of rosiglitazone in N-methyl-N-nitrosourea-induced mammary carcinogenesis in rats. N-methyl-N-nitrosourea was administered in two intraperitoneal doses each per 50 mg/kg b.w. between 40th and 51st postnatal days. Rosiglitazone was administered in a diet at a concentration of 10 ppm and 100 ppm, respectively, 9 days before the first carcinogen dose until the termination of the experiment. During the experiment the animals were weekly weighed and palpated for the presence of mammary tumors and estimation of latency period, tumor frequency per group and animal, and tumor volume were recorded. The experiment was terminated 16 weeks after the first carcinogen dose, basic tumor growth parameters and selected metabolic and hormonal variables were evaluated. Chemoprevention with higher rosiglitazone dose decreased tumor frequency per group by 44%, other tumor parameters (incidence, tumor frequency per animal) were decreased insignificantly (at both doses), latency period was not changed. Rosiglitazone administration decreased cumulative tumor volume, more efficiently at lower dose. Glycaemia and insulinaemia decreased after lower rosigitazone dose administration but glycaemia did not exceed normal values. Higher rosiglitazone dose alleviated some metabolic alterations resulting from cancer progression more effectively but induced a prominent cardiac hypertrophy.