Thiazolidinediones enhance vascular endothelial growth factor expression and induce cell growth inhibition in non-small-cell lung cancer cells

Background. it is known that thiazolidinediones are involved in regulating the expression of various genes,including the vascular endothelial growth factor (vegf) gene via peroxisome proliferator-activated receptor (ppar); vegf is a prognostic biomarker for non-small-cell lung cancer (nsclc). methods. 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. results. 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 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. conclusions. 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. © 2010 yoshizaki et al; licensee biomed central ltd.