The effect of PPAR-gamma agonists on lung cancer and their relationship to the NF-kappa B pathway

The nuclear factor-kappa B (NFkappaB) transcription factor is often overexpressed in lung cancer, resulting in blocked apoptotic pathways and an induction of chemoresistance. In this study, non-small cell lung cancer (NSCLC) cell lines were treated with PPARgamma-selective agonists to identify whether these agonists could inhibit lung cancer growth and NFkappaB-dependent pathways. We found that all agonists decreased lung cancer growth, with PGJ 2 being the most effective. NSCLC cells treated with PPARgamma agonists had a reduction in NFkappaB activity, as assessed through an NFkappaB reporter assay. Cell cycle analysis revealed that all agonists could significantly decrease the percentage of cells in S phase, and PGJ2 specifically could promote apoptosis as well. Further analysis with gene arrays revealed that NFkappaB-dependent cancer genes and transcription factors were reduced in agonist-treated cells. In conclusion, PPARgamma-agonists inhibit lung cancer growth by a variety of mechanisms and should be evaluated further for their therapeutic potential.