Rosuvastatin in the chemoprevention of N-methyl-N-nitrosourea-induced mammary carcinogenesis in female rats

Abstract

The results of preclinical research have indicated anticarcinogenic effects of statins in diverse tumors including breast cancer. Lipophilic atorvastatin and simvastatin have demonstrated high anticarcinogenic effects in experimental breast cancer in our previous experiments. In this study, the chemopreventive potential of hydrophilic rosuvastatin in N-methyl-N-nitrosourea induced mammary carcinogenesis in female rats was evaluated. Chemoprevention started 7 days before carcinogen administration and subsequently continued 17 weeks - until the end of the experiment. Dietary administered rosuvastatin (250 mg/kg) decreased tumor frequency by 39% (p=0.146), average tumor volume by 64% (p=0.236), as well as lengthened the latency period by 11 days (p=0.143) compared to controls. Moreover, rosuvastatin (250 mg/kg) decreased average tumor volume by 85% (p=0.0082) compared to the group with rosuvastatin at lower dose in the diet (25 mg/kg). A histopathological analysis of mammary tumors has revealed a shift from poorly differentiated to well differentiated tumors after treatment with rosuvastatin (250 mg/kg).With the exception of HDL-cholesterol, the parameters of plasma lipid metabolism did not differ after rosuvastatin treatment. Rosuvastatin did not change the food intake and body weight in rats. This study is the first about rosuvastatin used in rat mammary carcinogenesis. Hydrophilic rosuvastatin have shown lower antineoplastic activity than lipophilic statins in this model of experimental breast cancer.