title: Simvastatin Induces Apoptosis and Suppresses Insulin-Like Growth Factor 1 Receptor in Bile Duct Cancer Cells.
abstract: OBJECTIVE
  Statins act as antineoplastic agents through the inhibition of cell proliferation. This study sought to demonstrate the effects of statins on extrahepatic bile duct cancer cell apoptosis and to document the changes in protein expression involved in tumor growth and suppression.
  
  
  METHODS
  Human extrahepatic bile duct cancer cells were cultured. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays were performed to determine the effect of statins on cell proliferation. Apoptosis was measured by a cell death detection enzyme-linked immunosorbent assay and caspase-3 activity assay, and flow cytometry was used to determine the percentage of cells in each phase of the cell cycle. The protein expression of Bax, Bcl-2, insulin-like growth factor 1 (IGF-1) receptor, extracellular signal-regulated kinase 1/2 (ERK1/2), and Akt was measured by Western blot analysis.
  
  
  RESULTS
  Simvastatin suppressed cell proliferation by inducing G1 phase cell cycle arrest in bile duct cancer cells. Furthermore, it induced apoptosis via caspase-3 activation, downregulated the expression of the Bcl-2 protein, and enhanced the expression of the Bax protein. Moreover, simvastatin suppressed the expression of the IGF-1 receptor and IGF-1-induced ERK/Akt activation.
  
  
  CONCLUSIONS
  Simvastatin induces apoptosis in bile duct cancer cells, which suggests that it could be an antineoplastic agent for bile duct cancer.
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Hallym University College of Medicine, Hwaseong, Korea.
authors.forename: Jin
authors.initials: J
authors.lastname: Lee
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Hallym University College of Medicine, Hwaseong, Korea.
authors.forename: Eun Mi
authors.initials: EM
authors.lastname: Hong
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Hallym University College of Medicine, Hwaseong, Korea.
authors.forename: Ju Ah
authors.initials: JA
authors.lastname: Jang
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Hallym University College of Medicine, Hwaseong, Korea.
authors.forename: Se Woo
authors.initials: SW
authors.lastname: Park
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Hallym University College of Medicine, Hwaseong, Korea.
authors.forename: Dong Hee
authors.initials: DH
authors.lastname: Koh
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Hallym University College of Medicine, Hwaseong, Korea.
authors.forename: Min Ho
authors.initials: MH
authors.lastname: Choi
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Hallym University College of Medicine, Hwaseong, Korea.
authors.forename: Hyun Joo
authors.initials: HJ
authors.lastname: Jang
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Hallym University College of Medicine, Hwaseong, Korea.
authors.forename: Sea Hyub
authors.initials: SH
authors.lastname: Kae
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D001650:Bile Duct Neoplasms / Q000188:drug therapy*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D017526:Receptor, IGF Type 1 / Q000187:drug effects*; D019821:Simvastatin / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D000960:Hypolipidemic Agents; D019821:Simvastatin; D017526:Receptor, IGF Type 1
keywords: Apoptosis; Bax; Bile duct neoplasms; Receptor, IGF type 1; Simvastatin