title: Preventive effects of fluvastatin in rat mammary carcinogenesis.
abstract: On the basis of preclinical and clinical evidence, statins lead to risk reduction of several types of neoplasia including breast cancer. This study is the first report on the preventive effects of fluvastatin in experimental breast cancer in vivo. In this experiment, the antineoplastic effects of fluvastatin in the chemoprevention of N-methyl-N-nitrosourea-induced mammary carcinogenesis in female rats were evaluated. The effects of fluvastatin on selected parameters of apoptosis, proliferation, and angiogenesis in mammary tumor cells were determined. The drug was dietary administered at two concentrations of 20 and 200 mg/kg. The experiment was terminated 17 weeks after carcinogen administration; mammary tumors were removed and prepared for histomorphological and immunohistochemical analysis. The basic parameters of experimental carcinogenesis, chosen metabolic variables, and side effects after long-term fluvastatin treatment in animals were assessed. Fluvastatin at higher concentrations suppressed tumor frequency by 63% and tumor incidence by 33% in comparison with the controls. After fluvastatin treatment, immunohistochemical analysis of tumor cells showed a decrease in vascular endothelial growth factor receptor-2 expression by 86% and an increase in caspase-3 by 8.5%. Fluvastatin in both treated groups significantly increased the parameters of serum lipid metabolism and significantly decreased femur compact bone thickness and body weight in animals. Our results suggest that fluvastatin and other statins should be further evaluated for tumor-preventive characteristics.
authors.affiliation: Department of Medical Biology, Jessenius Faculty of Medicine, Comenius University, Martin, Slovakia. kubatka@jfmed.uniba.sk
authors.forename: Peter
authors.initials: P
authors.lastname: Kubatka
authors.forename: Nadežda
authors.initials: N
authors.lastname: Stollárová
authors.forename: Jozef
authors.initials: J
authors.lastname: Škarda
authors.forename: Katarína
authors.initials: K
authors.lastname: Žihlavníková
authors.forename: Karol
authors.initials: K
authors.lastname: Kajo
authors.forename: Andrea
authors.initials: A
authors.lastname: Kapinová
authors.forename: Katarína
authors.initials: K
authors.lastname: Adamicová
authors.forename: Martin
authors.initials: M
authors.lastname: Péč
authors.forename: Dušan
authors.initials: D
authors.lastname: Dobrota
authors.forename: Bianka
authors.initials: B
authors.lastname: Bojková
authors.forename: Monika
authors.initials: M
authors.lastname: Kassayová
authors.forename: Peter
authors.initials: P
authors.lastname: Orendáš
mesh_terms: D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D000077340:Fluvastatin; D007150:Immunohistochemistry; D007211:Indoles / Q000494:pharmacology* / Q000627:therapeutic use; D019394:Ki-67 Antigen / Q000032:analysis; D015674:Mammary Neoplasms, Animal / Q000473:pathology / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000032:analysis
chemical_list: D016588:Anticarcinogenic Agents; D005229:Fatty Acids, Monounsaturated; D007211:Indoles; D019394:Ki-67 Antigen; D000077340:Fluvastatin; D040301:Vascular Endothelial Growth Factor Receptor-2