Rosiglitazone reduces cell invasiveness by inducing MKP-1 in human U87MG glioma cells
Journal
Cancer Letters
Journal Volume
277
Journal Issue
2
Pages
141-148
Date Issued
2009
Author(s)
Abstract
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-γ 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. ? 2008 Elsevier Ireland Ltd. All rights reserved.
Subjects
Glioma; Matrix metalloproteinase; Mitogen activated protein kinase phosphatase-1
SDGs
Other Subjects
gelatinase A; mitogen activated protein kinase phosphatase 1; peroxisome proliferator activated receptor gamma; rosiglitazone; small interfering RNA; triptolide; article; cancer invasion; cell invasion; controlled study; drug inhibition; enzyme activity; enzyme release; glioma; human; human cell; priority journal; protein expression; signal transduction; Cell Line, Tumor; Dual Specificity Phosphatase 1; Glioma; Humans; Matrix Metalloproteinase 2; Neoplasm Invasiveness; PPAR gamma; Signal Transduction; Thiazolidinediones
Type
journal article