Antineoplastic effects of simvastatin in experimental breast cancer

Department of Medical Biology, Jessenius Faculty of Medicine, Comenius University, Martin, Slovak Republic.
Klinická onkologie: casopis Ceské a Slovenské onkologické spolecnosti 01/2011; 24(1):41-5.
Source: PubMed


Statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) have proven therapeutic and preventive effects on cardiovascular diseases. Preclinical evidence demonstrates tumor-suppressive effects of statins in several human neoplasias, including breast cancer.
In this study, antineoplastic effects of simvastatin in chemoprevention of N-methyl-N-nitrosourea-induced mammary carcinogenesis in female rats were evaluated. The drug was dietary administered at two concentrations--18 mg/kg (SIMVA 18) and 180 mg/kg (SIMVA 180).
Basic parameters of experimental carcinogenesis after long-term simvastatin treatment in animals were assessed. In the SIMVA 180 group, simvastatin significantly suppressed tumour frequency by 80.5% and tumour incidence by 58.5% in comparison to the controls. Higher dose simvastatin non-significantly decreased the mean tumor volume by 23.5%, as well as non-significantly lengthened the latency period by 14.5 days compared to the control animals. Simvastatin, administered at a lower dose did not change parameters of mammary carcinogenesis in comparison to the control group. Simvastatin in both treated groups significantly decreased serum levels of triacylglycerols and VLDL-cholesterol in comparison to the control animals. Compared to the controls, a significant increase in food intake by the animals was recorded in the SIMVA 18 and SIMVA 180 groups. No significant differences in the final body weight gain between the simvastatin-administered and the control group were found.
This study represents the first report of simvastatin use in experimental mammary carcinogenesis in vivo.

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Available from: Peter Kubatka
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    • "In the experiment of Lubet et al. (2009), atorvastatin and lovastatin did not change serum triglyceride levels in rat mammary carcinogenesis. Contrary to these results, simvastatin (18 and 180 mg/kg) significantly decreased the levels of triacylglycerols and VLDLcholesterol in comparison with the controls in rat mammary carcinogenesis (Kubatka et al., 2011c). Interestingly, atorvastatin (10 mg/kg), simvastatin (180 mg/kg), and rosuvastatin (250 mg/kg) significantly decreased serum HDLcholesterol in our experiments what is in contrast with the results in clinical trials, where the increase of this lipoprotein fraction ranged from 5 to 15% (Scandinavian simvastatin survival study, 1994; PROSPER study group, 2002). "
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