RRC ID 63390
Author Yang SH, Lin HY, Changou CA, Chen CH, Liu YR, Wang J, Jiang X, Luh F, Yen Y.
Title Integrin β3 and LKB1 are independently involved in the inhibition of proliferation by lovastatin in human intrahepatic cholangiocarcinoma.
Journal Oncotarget
Abstract Human intrahepatic cholangiocarcinomas are one of the most difficult cancers to treat. In our study, Lovastatin, a 3-hydroxy-3-methylglutaryl-coenzyme-CoA (HMG-CoA) reductase inhibitor, demonstrated anticancer properties by inhibiting cancer cell proliferation, cell migration and cell adhesion. Lovastatin inhibited the expressions of transforming growth factor (TGF)-β1, cyclooxygenase (COX)-2, and intercellular adhesion molecule (ICAM)-1. Furthermore, lovastatin inhibited the expressions of integrin β1 and integrin β3 but not integrin αv or integrin β5. While Lovastatin's inhibitory effects on TGFβ1, COX2, and ICAM-1 expression were independently controlled by the tumor suppressor LKB1, integrin β3 expression was not affected. Lovastatin's inhibitory effect on cell adhesion was associated with the decreased expression of integrin β3 and cell surface heterodimer integrin αvβ3. Quantitative real time PCR, fluorescent microscopy, and cell migration assays all confirmed that Lovastatin inhibits integrin αvβ3 downstream signaling including FAK activation, and β-catenin, vimentin, ZO-1, and β-actin. Overall, Lovastatin reduced tumor cell proliferation and migration by modifying the expression of genes involved in cell adhesion and other critical cellular processes. Our study highlights novel anti-cancer properties of Lovastatin and supports further exploration of statins in the context of cholangiocarcinoma therapy.
Volume 7(1)
Pages 362-73
Published 2016-1-5
DOI 10.18632/oncotarget.6238
PII 6238
PMID 26517522
PMC PMC4808004
MeSH AMP-Activated Protein Kinase Kinases Bile Duct Neoplasms / genetics Bile Duct Neoplasms / metabolism Bile Duct Neoplasms / pathology Cell Adhesion / drug effects Cell Adhesion / genetics Cell Line, Tumor Cell Movement / drug effects Cell Movement / genetics Cell Proliferation / drug effects* Cell Proliferation / genetics Cholangiocarcinoma / genetics Cholangiocarcinoma / metabolism Cholangiocarcinoma / pathology Gene Expression Regulation, Neoplastic / drug effects Humans Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology Immunoblotting Integrin beta3 / genetics* Integrin beta3 / metabolism Lovastatin / pharmacology* Microscopy, Confocal Microscopy, Fluorescence Protein Serine-Threonine Kinases / genetics* Protein Serine-Threonine Kinases / metabolism RNA Interference Reverse Transcriptase Polymerase Chain Reaction Signal Transduction / drug effects Signal Transduction / genetics beta Catenin / genetics beta Catenin / metabolism
IF 5.168
Human and Animal Cells RBE(RCB1292) HuH-28(RCB1943)