Melatonin potentiates the anti‐tumour effect of pravastatin in rat mammary gland carcinoma model

Summary Oncological research indicated a possible role of statins in the risk reduction of certain malignancies. The purpose of this experiment was to examine the chemopreventive effects of pravastatin alone and in combination with pineal hormone melatonin in the model of N‐methyl‐N‐nitrosourea‐induced mammary carcinogenesis in female rats. Pravastatin was administered dietary (100 mg/kg) and melatonin in a water solution (20 μg/ml). Chemoprevention began 7 days prior to carcinogen administration and subsequently continued 15 weeks until to 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‐term 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 9 days compared with control animals. High‐/low‐grade carcinomas ratio was apparently reduced in both treated groups. The analysis of carcinoma cells showed significant expression increase in caspase‐3 and caspase‐7 after pravastatin treatment; however, combined treatment increased the expression of both caspases even more pronounced. Regarding VEGFR‐2 expression, mild anti‐angiogenic effect in ca...
Source: International Journal of Experimental Pathology - Category: Pathology Authors: Tags: Original Article Source Type: research