Potential Molecular Targets of Statins in the Prevention of Hepatocarcinogenesis
Journal Title: Annals of Hepatology - Year 2018, Vol 17, Issue 3
Abstract
Hepatocellular carcinoma (HCC) represents 90% of liver tumors. Statins, may reduce the incidence of various tumors, including HCC. Antitumoral activities may be mediated by changes in transforming growth factor-beta (TGF-β1) and thyroid hormones (TH) regulation. Aim. The aim of our study is to establish the statins mechanism of action and the potential key molecules involved in an in vivo and in vitro HCC model. Materials and methods. We used two models: in vivo (in rats) using diethylnitrosamine (DEN) and hexachlorobenzene (HCB) to develop HCC, we analyzed cell proliferation parameters (proliferating cell nuclear antigen, PCNA) and cholesterol metabolism (hydroxy-methylglutaryl-CoA reductase, HMGCoAR). In vitro (Hep-G2 cells) we evaluated the effects of different doses of Atorvastatin (AT) and Simvastatin (SM) on HCB induced proliferation and analyzed proliferative parameters, colesterol metabolism, TGF-β1 mRNA, c-Src and TH levels. Results. In vivo, we observed that cell proliferation significantly increased as well as cholesterol serum levels in rats treated with HCB. In vitro, we observed the same results on PCNA as in vivo. The statins prevented the increase in HMG-CoAR mRNA levels induced by HCB, reaching levels similar to controls at máximum doses: AT (30 μM), and SM (20 μM). Increases in PCNA, TGF-β1, and pc-Src, and decreases in deiodinase I mRNA levels induced by HCB were not observed when cells were pre-treated with AT and SM at maximum doses. Conclusion. Statins can prevent the proliferative HCB effects on Hep-G2 cells. TGF-β1, c-Src and TH may be the statins molecular targets in hepatocarcinogenesis.<br/><br/>
Authors and Affiliations
Ezequiel Ridruejo, Giselle Romero-Caími, María J. Obregón, Diana Kleiman de Pisarev, Laura Alvarez
Keywords
Related Articles
- EP ID EP345416
- DOI 10.5604/01.3001.0011.7394
- Views 100
- Downloads 0
Thymosin β10 as a predictive biomarker of response to 5-fluorouracil chemotherapy in cholangiocarcinoma
Introduction and aim. 5-Fluorouracil (5-FU) is the most commonly used chemotherapeutic drug in the treatment of cholangiocarcinoma (CCA). Since development of drug resistance to 5-FU in CCA patients is the primary cause...
Genetic and Epigenetic Profile of Patients With Alcoholic Liver Disease
Alcoholic liver disease (ALD) is a definition encompassing a spectrum of disorders ranging from simple steatosis to cirrhosis and hepatocellular carcinoma. Excessive alcohol consumption triggers a series of metabolic rea...
Can ARFI elastography predict the presence of significant esophageal varices in newly diagnosed cirrhotic patients?
Aim. To establish an algorithm which includes the liver stiffness (LS) and/or spleen stiffness (SS) assessed by ARFI for the prediction of significant esophageal varices-EV (at least grade 2). Material and methods. Our...
Use of proteomic analysis tools to identify HCV-proteins down-regulated by acetylsalicylic acid
Background and aim. Acetylsalicylic acid (ASA) has been shown to downregulate HCV expression; however, the involved mechanisms are unknown. We used proteomic analysis to compare protein expression profiles between human...
Hepatocellular carcinoma that arose from primary Sjögren’s syndrome
Hepatocellular carcinoma (HCC) typically originates from HBV or HCV associated liver cirrhosis. Primary Sjögren’s syndrome (pSS) is a kind of autoimmune disease. A sixty-two year old female patient with mild liver damage...