Hepatocellular carcinoma (HCC) represents approximately 85% of all primary
liver cancer cases. Non-
alcoholic fatty liver disease (
NAFLD) is one of the risk factors for HCC.
NAFLD occurs in patients with components of
metabolic syndrome, such as type 2
diabetes mellitus,
obesity,
hypertension and
hyperlipidemia. Therefore,
hyperlipidemia also represents a patient population at risk for HCC that can readily be identified.
Rosuvastatin, a 3-hydroxy-3-methyl-glutaryl coenzyme A (
HMG-CoA) reductase inhibitor, has exhibited a more potent affinity for the active site of
HMG-CoA reductase than other
statins. In addition, the hepatic uptake of
rosuvastatin in rats has been found to be more selective and efficient than that with other drugs. Furthermore, the cytoprotective effects of
rosuvastatin against ischemic injury have been clearly reported. Thus, in this study, we aimed to determine the role of
rosuvastatin as a preventive drug in HCC associated with
NAFLD. STAM mice, which developed HCC from
NAFLD by being fed a high-fat diet (HFD), were divided into a group in which a HFD was given to the mice for 15 weeks (n=8) and another in which a HFD supplemented with 0.00125% rosuvastatin was given to the mice for 15 weeks (n=8).
Rosuvastatin inhibited the development of hepatic
tumors in the mice with
NAFLD induced by a specific diet both macroscopically and histologically.
Rosuvastatin significantly decreased the expression levels of pro-inflammatry
cytokines, such as
tumor necrosis factor (TNF)-α, interleukin (IL)-6 and transforming growth factor (TGF)-β1.
Tumor aggressiveness is mediated by angiogenic factors. Therefore, we examined the hepatic
mRNA expression of
vascular endothelial growth factor receptor (VEGFR),
epidermal growth factor receptor (EGFR) and platelet-derived growth factor (PDGF). The hepatic expression of these factors significantly decreased in the rousvastin-fed mice. Our results thus suggest
rosuvastatin that prevents
carcinogenesis and improves the hepatic background. Our data suggest that
rosuvastatin has potential for use as a preventive drug for the development of HCC associated with
NAFLD in mice.