Pravastatin inhibits cell proliferation and increased MAT1A expression in hepatocarcinoma cells and in vivo models

We design in vitro and in vivo model. In vitro we used PLC and determine cell proliferation. In vivo, we used and animal model to determined, PCNA and MAT1A expression and transaminases levels.We found that pravastatin decreases cell proliferation in vitro (cell proliferation in pravastatin group was 82%, in sorafenib group 51% and in combined group 40%) and in vivo (in pravastatin group 80%, in sorafenib group 76.4% and in combined group 72.72%). The MAT1A levels, was significantly higher in Pravastatin group (D 62%, P 94%, S 71%, P + S 91%). The transaminases levels, decreased significantly in Pravastatin group (GOT and GPT levels D 619.5 U/L; 271 U/L) (P 117.5 U/L; 43.5 U/L) (S 147 U/L; 59 U/L) (P + S 142 U/L; 59 U/L).The combination of pravastatin + sorafenib were more effective than Sorafenib alone.Hepatocellular carcinoma (HCC) is the fifth most common malignancy worldwide. It ranks third place in the list of malignancies leading to death [1] and the incidence of HCC has increased in eastern Asia, Europe and the United States [2]. Clinically, HCC is characterized by its invasiveness, poor prognosis and limited therapeutic opportunities. In many patients, HCC is diagnosed at an advanced stage. For these patients, the US Food and Drug Administration has approved the multikinase inhibitor, sorafenib [3,4]. In recent years, two studies have been published [5,6] which demonstrate that pravastatin increases the survival of patients with advanced hepatocellular cancer alone or in combination with chemoembolization.The molecular pathogenesis of HCC is complex and involves the abnormal clonal expansion of dysplastic hepatocytes, anti-apoptotic signalling and the stimulation of angiogenesis-associated growth factors [7].Today, statins are regarded as attractive molecules and they may affect cancer. Statins, the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, are a class of drugs that inhibit the rate-limiting step in the cholesterol biosynthesis pa