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 gamma (PPARgamma); 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 PPARgamma 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.
Yoshizaki
Takayuki
T
Innovation Center, Kagoshima University, 1-21-40 Korimoto, Kagoshima 890-0065, Japan. k8255261@kadai.jp
Motomura
Wataru
W
Tanno
Sachie
S
Kumei
Shima
S
Yoshizaki
Yumiko
Y
Tanno
Satoshi
S
Okumura
Toshikatsu
T
D002289:Carcinoma, Non-Small-Cell Lung / Q000196:embryology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003470:Culture Media / Q000494:pharmacology; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology; D008175:Lung Neoplasms / Q000378:metabolism*; D039942:Neuropilin-1 / Q000096:biosynthesis; D047495:PPAR gamma / Q000378:metabolism; D010766:Phosphorylation; D012333:RNA, Messenger / Q000378:metabolism; D045162:Thiazolidinediones / Q000494:pharmacology*; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis*
D003470:Culture Media; D007004:Hypoglycemic Agents; D047495:PPAR gamma; D012333:RNA, Messenger; D045162:Thiazolidinediones; D042461:Vascular Endothelial Growth Factor A; D039942:Neuropilin-1; C039671:ciglitazone