Rosiglitazone reduces cell invasiveness by inducing MKP-1 in human U87MG glioma cells

Hsun Jin Jan, Chin Cheng Lee, Yu Min Lin, Jing Huei Lai, Hen Wei Wei, Horng Mo Lee

Research output: Contribution to journalArticle

16 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)141-148
Number of pages8
JournalCancer Letters
Volume277
Issue number2
DOIs
Publication statusPublished - May 18 2009

Keywords

  • Glioma
  • Matrix metalloproteinase
  • Mitogen activated protein kinase phosphatase-1

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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    Jan, H. J., Lee, C. C., Lin, Y. M., Lai, J. H., Wei, H. W., & Lee, H. M. (2009). Rosiglitazone reduces cell invasiveness by inducing MKP-1 in human U87MG glioma cells. Cancer Letters, 277(2), 141-148. https://doi.org/10.1016/j.canlet.2008.11.033