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

doi:10.1016/j.lungcan.2005.10.010

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

Department of Biomedical Sciences

Research output: Contribution to journal › Article › peer-review

88 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 language	English
Pages (from-to)	297-301
Number of pages	5
Journal	Lung Cancer
Volume	51
Issue number	3
DOIs	https://doi.org/10.1016/j.lungcan.2005.10.010
Publication status	Published - 2006 Mar

Keywords

EGFR
Gefitinib
PPAR-γ
PTEN
Rosiglitazone

ASJC Scopus subject areas

Oncology
Pulmonary and Respiratory Medicine
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.lungcan.2005.10.010

Cite this

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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 = mar,

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",

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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

Y1 - 2006/3

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

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JO - Lung Cancer

JF - Lung Cancer

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ER -

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

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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