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The purpose of these studies was to examine the chemopreventive effects of pravastatin alone and in combination with pineal hormone melatonin in the <jats:italic>N<\/jats:italic>\u2010methyl\u2010<jats:italic>N<\/jats:italic>\u2010nitrosourea\u2010induced mammary carcinogenesis model. Pravastatin was given orally (1 00\u00a0mg\/kg) and melatonin was added to the water (20\u00a0\u03bcg\/ml). Chemoprevention began seven\u00a0days prior to carcinogen administration and subsequently continued for 15\u00a0weeks until autopsy. At autopsy, mammary tumours were removed and prepared for histopathological and immunohistochemical analysis. Parameters of experimental carcinogenesis, mechanism of action (biomarkers of apoptosis, angiogenesis and proliferation) and side effects after long\u2010term treatment in animals were assessed. Pravastatin alone suppressed tumour frequency by 20.5% and average tumour volume by 15% compared with controls. Combined administration of the drugs decreased tumour frequency by 69% and lengthened tumour latency by nine\u00a0days compared with control animals. The ration between high and low grade carcinomas was apparently reduced in both treated groups. The analysis of carcinoma cells showed significant expression increase in caspase\u20103 and caspase\u20107 after pravastatin treatment; however, combined treatment even more pronounced increase in the expression of both caspases. Regarding <jats:styled-content style=\"fixed-case\">VEGFR<\/jats:styled-content>\u20102 expression, a small effect in carcinomas of both treated groups was found. In plasma metabolism evaluation, pravastatin alone significantly decreased levels of glucose and triacylglycerols. Our results suggest a mild anti\u2010neoplastic effect of pravastatin in this rat mammary gland carcinoma model. Statins co\u2010administered with other suitable drug (e.g. melatonin) should be further evaluated for tumour\u2010preventive properties.<\/jats:p>","DOI":"10.1111\/iep.12094","type":"journal-article","created":{"date-parts":[[2014,10,1]],"date-time":"2014-10-01T06:13:48Z","timestamp":1412144028000},"page":"401-410","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Melatonin potentiates the anti\u2010tumour effect of pravastatin in rat mammary gland carcinoma model"],"prefix":"10.1111","volume":"95","author":[{"given":"Peter","family":"Orend\u00e1\u0161","sequence":"first","affiliation":[{"name":"Department of Animal Physiology Institute of Biological and Ecological Sciences Faculty of Science P. 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