%0 Journal Article
%T Thiazolidinediones enhance vascular endothelial growth factor expression and induce cell growth inhibition in non-small-cell lung cancer cells
%A Takayuki Yoshizaki
%A Wataru Motomura
%A Sachie Tanno
%A Shima Kumei
%A Yumiko Yoshizaki
%A Satoshi Tanno
%A Toshikatsu Okumura
%J Journal of Experimental & Clinical Cancer Research
%D 2010
%I BioMed Central
%R 10.1186/1756-9966-29-22
%X In this study, we investigated the effects of troglitazone and ciglitazone on the mRNA expression of VEGF and its receptors in human NSCLC cell lines, RERF-LC-AI, SK-MES-1, PC-14, and A549. These mRNA expressions were evaluated by quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR) analysis. We also studied the effect of Je-11, a VEGF inhibitor, on the growth of these cells.In NSCLC cells, thiazolidinediones increased the mRNA expression of VEGF and neuropilin-1, but not that of other receptors such as fms-like tyrosine kinase and kinase insert domain receptor-1. Furthermore, the PPAR¦Ã antagonist GW9662 completely reversed this thiazolidinedione-induced increase in VEGF expression. Furthermore, the addition of VEGF inhibitors into the culture medium resulted in the reversal of thiazolidinedione-induced growth inhibition.Our results indicated that thiazolidinediones enhance VEGF and neuropilin-1 expression and induce the inhibition of cell growth. We propose the existence of a pathway for arresting cell growth that involves the interaction of thiazolidinedione-induced VEGF and neuropilin-1 in NSCLC.Peroxisome proliferator-activated receptor ¦Ã (PPAR¦Ã) belongs to a family of ligand-activated transcription factors. PPAR¦Ã is an intracellular sensor for fatty acids and fatty acid derivatives, which in turn act as endogenous ligands for PPAR¦Ã. PPAR¦Ã and its ligand activators regulate several lipid and glucose metabolism pathways [1].In humans, PPAR¦Ã is expressed in multiple tissues, including the breast, colon, prostate, lung, placenta, and pituitary tissues [2-5]. PPAR¦Ã activation is antiproliferative by virtue of its differentiation-promoting effects. For example, ligands activating PPAR¦Ã were effective in arresting the growth of dedifferentiated tumor cells in multiple tumor types [2,4-9], and they promoted differentiation of tumor cells and inhibited spontaneous metastasis in a xenograft model [7]. However, the mechanism by which PPAR¦Ã arres
%U http://www.jeccr.com/content/29/1/22