Gut Liver.  2016 Mar;10(2):310-317. 10.5009/gnl15195.

Simvastatin Induces Apoptosis and Suppresses Insulin-Like Growth Factor 1 Receptor in Bile Duct Cancer Cells

• Lee J
• Hong EM
• Jang JA
• Park SW
• Koh DH
• Choi MH
• Jang HJ
• Kae SH

• KMID: 2363978
• DOI: http://doi.org/10.5009/gnl15195

Abstract

BACKGROUND/AIMS
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.

Keyword

Simvastatin; Bile duct neoplasms; Apoptosis; Receptor; IGF type 1; Bax

MeSH Terms

Antineoplastic Agents/pharmacology
Apoptosis/*drug effects
Bile Duct Neoplasms/*drug therapy
Cell Cycle/drug effects
Cell Line, Tumor
Cell Proliferation/drug effects
Enzyme-Linked Immunosorbent Assay
Flow Cytometry
Humans
Hypolipidemic Agents/*pharmacology
Receptor, IGF Type 1/*drug effects
Simvastatin/*pharmacology
Antineoplastic Agents
Hypolipidemic Agents
Receptor, IGF Type 1
Simvastatin