title: Simvastatin induces growth inhibition and apoptosis in HepG2 and Huh7 hepatocellular carcinoma cells via upregulation of Notch1 expression.
abstract: 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.
authors.affiliation: Department of General Surgery, Xi'an Central Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi 710003, P.R. China.
authors.forename: Xin
authors.initials: X
authors.lastname: Huang
authors.affiliation: Department of General Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.
authors.forename: Jiancang
authors.initials: J
authors.lastname: Ma
authors.affiliation: Department of General Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.
authors.forename: Jinkai
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of General Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Su
authors.affiliation: Department of General Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhao
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D055785:Gene Knockdown Techniques; D056945:Hep G2 Cells; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D051881:Receptor, Notch1 / Q000235:genetics* / Q000378:metabolism; D019821:Simvastatin / Q000494:pharmacology*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D012333:RNA, Messenger; D051881:Receptor, Notch1; D016159:Tumor Suppressor Protein p53; D019821:Simvastatin; D051057:Proto-Oncogene Proteins c-akt