Rosiglitazone reduces cell invasiveness by inducing MKP-1 in human U87MG glioma cells.
We sought to investigate the molecular mechanisms by which rosiglitazone (RGZ) inhibits cell invasion in human glioma cells. In this study, we found that RGZ attenuated MMP-2 protein levels, MMP-2 gelatinolytic activity, and cell invasiveness through a PPAR-gamma independent pathway. RGZ increased mitogen activated protein kinase phosphatase-1 (MKP-1) expression. The addition of triptolide (a diterpenoid triepoxide, which blocked MKP-1 induction) abolished the inhibitory effects by RGZ. Furthermore, we demonstrated that the knock down of MKP-1 by MKP-1 specific small interference RNA reversed the reduction of MMP-2 secretion, and of cell invasiveness by RGZ. In contrast, the stable expression of MKP-1 in glioma cell lines decreased MMP-2 activity and cell invasiveness. These results suggest that RGZ may mediate the inhibitory effects through MKP-1 induction. Thus, MKP-1 could be a potential target in glioma therapy.
Jan
Hsun-Jin
HJ
Graduate Institute of Medical Sciences, Taipei Medical University, 250 Wu-Hsing Street, Taipei, Taiwan.
Lee
Chin-Cheng
CC
Lin
Yu-Min
YM
Lai
Jing-Huei
JH
Wei
Hen-Wei
HW
Lee
Horng-Mo
HM
D045744:Cell Line, Tumor; D054638:Dual Specificity Phosphatase 1 / Q000378:metabolism*; D005910:Glioma / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D061965:Matrix Metalloproteinase Inhibitors; D009361:Neoplasm Invasiveness; D047495:PPAR gamma / Q000819:agonists*; D000077154:Rosiglitazone; D015398:Signal Transduction; D045162:Thiazolidinediones / Q000494:pharmacology*
D061965:Matrix Metalloproteinase Inhibitors; D047495:PPAR gamma; D045162:Thiazolidinediones; D000077154:Rosiglitazone; C517019:DUSP1 protein, human; D054638:Dual Specificity Phosphatase 1; D020778:Matrix Metalloproteinase 2