title: Rosiglitazone reduces cell invasiveness by inducing MKP-1 in human U87MG glioma cells.
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-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.
authors.affiliation: Graduate Institute of Medical Sciences, Taipei Medical University, 250 Wu-Hsing Street, Taipei, Taiwan.
authors.forename: Hsun-Jin
authors.initials: HJ
authors.lastname: Jan
authors.forename: Chin-Cheng
authors.initials: CC
authors.lastname: Lee
authors.forename: Yu-Min
authors.initials: YM
authors.lastname: Lin
authors.forename: Jing-Huei
authors.initials: JH
authors.lastname: Lai
authors.forename: Hen-Wei
authors.initials: HW
authors.lastname: Wei
authors.forename: Horng-Mo
authors.initials: HM
authors.lastname: Lee
mesh_terms: 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*
chemical_list: D061965:Matrix Metalloproteinase Inhibitors; D047495:PPAR gamma; D045162:Thiazolidinediones; D000077154:Rosiglitazone; C517019:DUSP1 protein, human; D054638:Dual Specificity Phosphatase 1; D020778:Matrix Metalloproteinase 2