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Statins, cholesterol‑lowering drugs, are one of the most commonly prescribed types of medications. Previous studies have suggested that simvastatin may inhibit the cell function and tumor growth of hepatocellular carcinoma (HCC) cells; however, the molecular mechanisms underlying simvastatin‑induced apoptosis in HCC cells remains to be elucidated. The aim of the present study was to investigate the role of simvastatin in the regulation of cell viability, proliferation and apoptosis in HepG2 and Huh7 HCC cells, and to elucidate the specific regulatory mechanisms by which simvastatin proceeds. MTT, trypan blue and flow cytometric analyses were performed in order to detect viability, proliferation and apoptosis in HepG2 and Huh7 cells. The results of the present study demonstrated that simvastatin significantly decreased cell viability and proliferation as well as increased apoptosis in HepG2 and Huh7 cells compared to that in untreated cells. In addition, reverse transcription quantitative polymerase chain reaction and western blot analysis revealed that simvastatin‑treated cells exhibited increased expression levles of Notch1, p53, and Bax, as well as decreased expression levels of B cell lymphoma 2; furthermore, Notch1 upregulation resulted in the inhibition of Akt phosphorylation. In conclusion, the results of the present study indicated that simvastatin significantly promoted apoptosis in HCC cells, the mechanism of which may have proceeded via the upregualtion of the Notch1 gene in the Akt‑dependent signaling pathway.

Objective: To establish a novel bioartificial liver (BAL) consisting of spheroids of porcine hepatocytes in a hollow-fiber bioreactor, and to perform an in vitro study on its metabolic effects on the serum from severe hepatitis B patients., Methods: Hepatocytes were isolated from pup pigs and cultured as aggregate spheroids through rotation and vibration. Phase-contrast microscopy, transmission electron microscopy, and scanning electron microscopy were used for morphological detection of hepatocyte spheroids. The hepatocyte spheroids were then transferred into the shell of a polysulfone hollow-fiber bioreactor, creating a novel BAL. Diluted serum samples of severe hepatitis B patients were circulated for 3 hours each into the bioreactor, by using an extracorporeal circulatory system. Every half hour, including both before and after perfusion, serum samples were collected to assay total bilirubin (TBIL), total protein (TP), albumin (ALB), and globulin (GLB) concentrations in order to judge the metabolic effects of this novel BAL., Results: Most hepatocytes had formed spheroids with high viability after 24 hours in culture. After 3 hours of perfusion, when compared with the control group, the serum concentration of TBIL in the treatment group decreased significantly (P < 0.01), but the serum concentrations of TP and ALB increased significantly (P < 0.05)., Conclusions: Hepatocytes can be conveniently cultured as aggregate spheroids through a rotation and vibration method. The novel BAL is efficient in removing bilirubin from the serum of severe hepatitis B patients, and in supplying the serum with ALB. Thus, the BAL might provide effective therapy for patients with severe hepatitis B.