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.

Original languageEnglish
Pages (from-to)362-373
Number of pages12
JournalOncotarget
Volume7
Issue number1
DOIs
Publication statusPublished - Jan 1 2016

Fingerprint

Lovastatin
Cholangiocarcinoma
Integrins
Cell Adhesion
Intercellular Adhesion Molecule-1
Neoplasms
Cell Movement
Cell Migration Assays
Cell Proliferation
Hydroxymethylglutaryl CoA Reductases
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Catenins
Coenzymes
Transforming Growth Factors
Vimentin
Cyclooxygenase 2
Actins
Real-Time Polymerase Chain Reaction
Microscopy
Gene Expression

Keywords

  • Bile duct cancer
  • HMG-CoA reductase inhibitor
  • Integrin
  • LKB1
  • TGF-β1

ASJC Scopus subject areas

  • Oncology

Cite this

Integrin β3 and LKB1 are independently involved in the inhibition of proliferation by lovastatin in human intrahepatic cholangiocarcinoma. / Yang, Sheng Huei; Lin, Hung Yun; Changou, Chun A.; Chen, Chun Han; Liu, Yun Ru; Wang, Jinghan; Jiang, Xiaoqing; Luh, Frank; Yen, Yun.

In: Oncotarget, Vol. 7, No. 1, 01.01.2016, p. 362-373.

Research output: Contribution to journalArticle

@article{2a4b147b736649efabed5b2702af416b,
title = "Integrin β3 and LKB1 are independently involved in the inhibition of proliferation by lovastatin in human intrahepatic cholangiocarcinoma",
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.",
keywords = "Bile duct cancer, HMG-CoA reductase inhibitor, Integrin, LKB1, TGF-β1",
author = "Yang, {Sheng Huei} and Lin, {Hung Yun} and Changou, {Chun A.} and Chen, {Chun Han} and Liu, {Yun Ru} and Jinghan Wang and Xiaoqing Jiang and Frank Luh and Yun Yen",
year = "2016",
month = "1",
day = "1",
doi = "10.18632/ONCOTARGET.6238",
language = "English",
volume = "7",
pages = "362--373",
journal = "Oncotarget",
issn = "1949-2553",
publisher = "Impact Journals LLC",
number = "1",

}

TY - JOUR

T1 - Integrin β3 and LKB1 are independently involved in the inhibition of proliferation by lovastatin in human intrahepatic cholangiocarcinoma

AU - Yang, Sheng Huei

AU - Lin, Hung Yun

AU - Changou, Chun A.

AU - Chen, Chun Han

AU - Liu, Yun Ru

AU - Wang, Jinghan

AU - Jiang, Xiaoqing

AU - Luh, Frank

AU - Yen, Yun

PY - 2016/1/1

Y1 - 2016/1/1

N2 - 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.

AB - 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.

KW - Bile duct cancer

KW - HMG-CoA reductase inhibitor

KW - Integrin

KW - LKB1

KW - TGF-β1

UR - http://www.scopus.com/inward/record.url?scp=84973405454&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84973405454&partnerID=8YFLogxK

U2 - 10.18632/ONCOTARGET.6238

DO - 10.18632/ONCOTARGET.6238

M3 - Article

C2 - 26517522

AN - SCOPUS:84973405454

VL - 7

SP - 362

EP - 373

JO - Oncotarget

JF - Oncotarget

SN - 1949-2553

IS - 1

ER -