Effect of simvastatin on c-myc, cyclin D1 and p53 expression in DMBA-induced breast cancer in mice
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.
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.
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.
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.
Breast cancer , Simvastatin , Cyclin D1 , C-myc , P53
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