title: PPAR-gamma 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-gamma (PPAR-gamma) 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-gamma 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-gamma and PTEN expression were found to have increased in the gefitinib- and rosiglitazone-treated cells. This suggests that PPAR-gamma agonist (rosiglitazone) potentiated gefitinib's anti-proliferative effects by increased of PTEN expression, and suggest that PPAR-gamma ligands may serve as potential therapeutic agents for NSCLC.
authors.affiliation: Department of Internal Medicine, Korea University, Guro Hospital, Seoul, Republic of Korea.
authors.forename: Sung Yong
authors.initials: SY
authors.lastname: Lee
authors.forename: Gyu Young
authors.initials: GY
authors.lastname: Hur
authors.forename: Ki Hwan
authors.initials: KH
authors.lastname: Jung
authors.forename: Hye Cheol
authors.initials: HC
authors.lastname: Jung
authors.forename: Sang Yeub
authors.initials: SY
authors.lastname: Lee
authors.forename: Je Hyeong
authors.initials: JH
authors.lastname: Kim
authors.forename: Chol
authors.initials: C
authors.lastname: Shin
authors.forename: Jae Jeong
authors.initials: JJ
authors.lastname: Shim
authors.forename: Kwang Ho
authors.initials: KH
authors.lastname: In
authors.forename: Kyung Ho
authors.initials: KH
authors.lastname: Kang
authors.forename: Se Hwa
authors.initials: SH
authors.lastname: Yoo
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D015153:Blotting, Western; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D000077156:Gefitinib; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D047495:PPAR gamma / Q000819:agonists; D051059:PTEN Phosphohydrolase / Q000378:metabolism*; D011799:Quinazolines / Q000494:pharmacology*; D000077154:Rosiglitazone; D018709:Statistics, Nonparametric; D045162:Thiazolidinediones / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D047495:PPAR gamma; D011799:Quinazolines; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D051059:PTEN Phosphohydrolase; D000077156:Gefitinib