Antitumor effects of atorvastatin in the chemoprevention of rat mammary carcinogenesis |
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Authors: | Peter Kubatka Katarína ?ihlavniková Peter Solár Karol Kajo Vanda Valentová Martin Pé? Bianka Bojková Monika Kassayová Nade?da Stollárová and Ivan Ahlers |
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Institution: | (1) Center for Cardiovascular Disease Prevention, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA; |
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Abstract: | Epidemiological studies indicate that 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, or statins, play a role
in inhibition of several human neoplasia including breast cancer. In this study, chemopreventive effects of atorvastatin in
N-methyl-N-nitrosourea-induced mammary carcinogenesis in female rats were evaluated. Atorvastatin was administered in the
diet at two concentrations: 10 mg/kg (ATOR 10) and 100 mg/kg (ATOR 100). Atorvastatin treatment began 8 days prior to carcinogen
administration and subsequently continued for 15 weeks till the end of the experiment. Atorvastatin at a higher dose suppressed
tumor frequency by 80.5% (P = 0.0008) and tumor incidence by 49.5% (P = 0.015), and extended latency period by 14 days (P = 0.076) when compared to the control group. Atorvastatin at a lower dose did not significantly alter tumor parameters in
comparison with the control group. In the specimens of mammary tumors, atorvastatin (in the ATOR 100 group) significantly
decreased mRNA expression of Bcl-2 gene but non-significantly increased Bax mRNA expression compared to control group. Atorvastatin
administration did not alter serum concentration of triacylglycerols, total cholesterol, and LDL cholesterol in comparison
with controls. This study is the first report on tumor suppressive effect of atorvastatin in rat mammary carcinogenesis. |
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