PPAR-γ agonist increase gefitinib's antitumor activity through PTEN expression

Sung Yong Lee, Gyu Young Hur, Ki Hwan Jung, Hye Cheol Jung, Sang Yeub Lee, Je Hyeong Kim, Chol Shin, Jae Jeong Shim, Kwang Ho In, Kyung Ho Kang, Se Hwa Yoo

Research output: Contribution to journalArticle

76 Citations (Scopus)

Abstract

Gefitinib exhibits antitumor activity in patient with non-small cell lung cancer (NSCLC). However, only 10-20% of patients exhibit clinical response to this drug. The molecular mechanisms underlying gefitinib sensitivity remain unknown. Peroxisome proliferators-activated receptor-γ (PPAR-γ) plays roles in the regulation of cellular differentiation and growth. This regulation was mediated by increasing Phosphatase and tensin homologue deleted on chromosome Ten (PTEN) levels. PTEN plays a role in the modulation of the phosphatidylinositol 3-kinase pathway (PI3K), which is involved in cell proliferation and survival. This study investigated the effects of PPAR-γ agonist (rosiglitazone) on the expression of PTEN, as well as EGFR tyrosine kinase inhibitor (gefitinib)'s antitumor activity in A549 cells. The treatment of A549 cells with rosiglitazone reduced the growth of A549 cells in a dose-dependent manner, and facilitated the anti-proliferative effects of gefitinib. PPAR-γ and PTEN expression were found to have increased in the gefitinib- and rosiglitazone-treated cells. This suggests that PPAR-γ agonist (rosiglitazone) potentiated gefitinib's anti-proliferative effects by increased of PTEN expression, and suggest that PPAR-γ ligands may serve as potential therapeutic agents for NSCLC.

Original languageEnglish
Pages (from-to)297-301
Number of pages5
JournalLung Cancer
Volume51
Issue number3
DOIs
Publication statusPublished - 2006 Mar 1

Fingerprint

rosiglitazone
Peroxisome Proliferator-Activated Receptors
Non-Small Cell Lung Carcinoma
Phosphatidylinositol 3-Kinase
Growth
Phosphoric Monoester Hydrolases
Protein-Tyrosine Kinases
gefitinib
Cell Survival
Chromosomes
Cell Proliferation
Ligands
Therapeutics
Pharmaceutical Preparations

Keywords

  • EGFR
  • Gefitinib
  • PPAR-γ
  • PTEN
  • Rosiglitazone

ASJC Scopus subject areas

  • Oncology

Cite this

PPAR-γ agonist increase gefitinib's antitumor activity through PTEN expression. / Lee, Sung Yong; Hur, Gyu Young; Jung, Ki Hwan; Jung, Hye Cheol; Lee, Sang Yeub; Kim, Je Hyeong; Shin, Chol; Shim, Jae Jeong; In, Kwang Ho; Kang, Kyung Ho; Yoo, Se Hwa.

In: Lung Cancer, Vol. 51, No. 3, 01.03.2006, p. 297-301.

Research output: Contribution to journalArticle

@article{646364ff5d8e44838cdd4c81b9fbbeda,
title = "PPAR-γ agonist increase gefitinib's antitumor activity through PTEN expression",
abstract = "Gefitinib exhibits antitumor activity in patient with non-small cell lung cancer (NSCLC). However, only 10-20{\%} of patients exhibit clinical response to this drug. The molecular mechanisms underlying gefitinib sensitivity remain unknown. Peroxisome proliferators-activated receptor-γ (PPAR-γ) plays roles in the regulation of cellular differentiation and growth. This regulation was mediated by increasing Phosphatase and tensin homologue deleted on chromosome Ten (PTEN) levels. PTEN plays a role in the modulation of the phosphatidylinositol 3-kinase pathway (PI3K), which is involved in cell proliferation and survival. This study investigated the effects of PPAR-γ agonist (rosiglitazone) on the expression of PTEN, as well as EGFR tyrosine kinase inhibitor (gefitinib)'s antitumor activity in A549 cells. The treatment of A549 cells with rosiglitazone reduced the growth of A549 cells in a dose-dependent manner, and facilitated the anti-proliferative effects of gefitinib. PPAR-γ and PTEN expression were found to have increased in the gefitinib- and rosiglitazone-treated cells. This suggests that PPAR-γ agonist (rosiglitazone) potentiated gefitinib's anti-proliferative effects by increased of PTEN expression, and suggest that PPAR-γ ligands may serve as potential therapeutic agents for NSCLC.",
keywords = "EGFR, Gefitinib, PPAR-γ, PTEN, Rosiglitazone",
author = "Lee, {Sung Yong} and Hur, {Gyu Young} and Jung, {Ki Hwan} and Jung, {Hye Cheol} and Lee, {Sang Yeub} and Kim, {Je Hyeong} and Chol Shin and Shim, {Jae Jeong} and In, {Kwang Ho} and Kang, {Kyung Ho} and Yoo, {Se Hwa}",
year = "2006",
month = "3",
day = "1",
doi = "10.1016/j.lungcan.2005.10.010",
language = "English",
volume = "51",
pages = "297--301",
journal = "Lung Cancer",
issn = "0169-5002",
publisher = "Elsevier Ireland Ltd",
number = "3",

}

TY - JOUR

T1 - PPAR-γ agonist increase gefitinib's antitumor activity through PTEN expression

AU - Lee, Sung Yong

AU - Hur, Gyu Young

AU - Jung, Ki Hwan

AU - Jung, Hye Cheol

AU - Lee, Sang Yeub

AU - Kim, Je Hyeong

AU - Shin, Chol

AU - Shim, Jae Jeong

AU - In, Kwang Ho

AU - Kang, Kyung Ho

AU - Yoo, Se Hwa

PY - 2006/3/1

Y1 - 2006/3/1

N2 - Gefitinib exhibits antitumor activity in patient with non-small cell lung cancer (NSCLC). However, only 10-20% of patients exhibit clinical response to this drug. The molecular mechanisms underlying gefitinib sensitivity remain unknown. Peroxisome proliferators-activated receptor-γ (PPAR-γ) plays roles in the regulation of cellular differentiation and growth. This regulation was mediated by increasing Phosphatase and tensin homologue deleted on chromosome Ten (PTEN) levels. PTEN plays a role in the modulation of the phosphatidylinositol 3-kinase pathway (PI3K), which is involved in cell proliferation and survival. This study investigated the effects of PPAR-γ agonist (rosiglitazone) on the expression of PTEN, as well as EGFR tyrosine kinase inhibitor (gefitinib)'s antitumor activity in A549 cells. The treatment of A549 cells with rosiglitazone reduced the growth of A549 cells in a dose-dependent manner, and facilitated the anti-proliferative effects of gefitinib. PPAR-γ and PTEN expression were found to have increased in the gefitinib- and rosiglitazone-treated cells. This suggests that PPAR-γ agonist (rosiglitazone) potentiated gefitinib's anti-proliferative effects by increased of PTEN expression, and suggest that PPAR-γ ligands may serve as potential therapeutic agents for NSCLC.

AB - Gefitinib exhibits antitumor activity in patient with non-small cell lung cancer (NSCLC). However, only 10-20% of patients exhibit clinical response to this drug. The molecular mechanisms underlying gefitinib sensitivity remain unknown. Peroxisome proliferators-activated receptor-γ (PPAR-γ) plays roles in the regulation of cellular differentiation and growth. This regulation was mediated by increasing Phosphatase and tensin homologue deleted on chromosome Ten (PTEN) levels. PTEN plays a role in the modulation of the phosphatidylinositol 3-kinase pathway (PI3K), which is involved in cell proliferation and survival. This study investigated the effects of PPAR-γ agonist (rosiglitazone) on the expression of PTEN, as well as EGFR tyrosine kinase inhibitor (gefitinib)'s antitumor activity in A549 cells. The treatment of A549 cells with rosiglitazone reduced the growth of A549 cells in a dose-dependent manner, and facilitated the anti-proliferative effects of gefitinib. PPAR-γ and PTEN expression were found to have increased in the gefitinib- and rosiglitazone-treated cells. This suggests that PPAR-γ agonist (rosiglitazone) potentiated gefitinib's anti-proliferative effects by increased of PTEN expression, and suggest that PPAR-γ ligands may serve as potential therapeutic agents for NSCLC.

KW - EGFR

KW - Gefitinib

KW - PPAR-γ

KW - PTEN

KW - Rosiglitazone

UR - http://www.scopus.com/inward/record.url?scp=33144483998&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33144483998&partnerID=8YFLogxK

U2 - 10.1016/j.lungcan.2005.10.010

DO - 10.1016/j.lungcan.2005.10.010

M3 - Article

C2 - 16386327

AN - SCOPUS:33144483998

VL - 51

SP - 297

EP - 301

JO - Lung Cancer

JF - Lung Cancer

SN - 0169-5002

IS - 3

ER -