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.
ASJC Scopus subject areas
- Pulmonary and Respiratory Medicine
- Cancer Research