Effect of simvastatin on c-myc, cyclin D1 and p53 expression in DMBA-induced breast cancer in mice

Introduction: Recently, the therapeutic and antioxidant effects of simvastatin on 7,12-dimethylbenz[a] anthracene (DMBA) induced breast cancer have been studied. To gain further understanding of the molecular mechanisms of simvastatin, this study investigated its effects on the expression of c-myc, cyclin D1 and p53 in normal mammary glands and tumors. Methods: Female albino mice were divided into two groups: 1) N group, healthy mice without DMBA and 2) D group, mice with DMBA administration. After the appearance of tumors, D group mice are subdivided into 3 groups, as control (C), simvastatin- treated group (S) which received 80 mg/kg/day, orally and tamoxifen-treated group (T) with 50 mg/kg/day, orally. After 4 weeks, animals were sacrificed. Also, the tumors and normal mammary glands were removed for histopathological evaluations and analysis of gene expression by qRT-PCR. Results: The results showed the up-regulation of c-myc and cyclin D1 in tumors of the control group compared with mammary glands of the N group. Similar to tamoxifen, the simvastatin treatment could normalize the expression of c-myc and cyclin D1; however, the expression of p53 did not change in the treated groups. Conclusion: Down-regulation of c-myc and cyclin D1 in treated tumors with simvastatin could be a possible molecular mechanism for its therapeutic effects in DMBA-induced breast cancer in mice.