Induced expression of MMP-9 in C6 glioma cells is inhibited by PDGF via a PI 3-kinase-dependent pathway

Biochem Biophys Res Commun. 2002 Aug 30;296(4):864-9. doi: 10.1016/s0006-291x(02)02008-9.


The involvement of phosphatidylinositol 3 (PI 3)-kinase in the signalling pathways leading to MMP-9 expression in glioma cells remains unclear. Here, we report that PI 3-kinase inhibits MMP-9 expression induced by either IL-1 or TNF-alpha in rat C6 glioma cells. Using zymography and semi-quantitative RT-PCR analysis, we showed that treatment of C6 cells with wortmannin, an inhibitor of PI 3-kinase activity, potentiated the expression of MMP-9 induced by both cytokines. In contrast, platelet-derived growth factor (PDGF), an inducer of PI 3-kinase activity in C6 cells, inhibited IL-1- or TNF-alpha-induced MMP-9 secretion. Accordingly, this inhibition by PDGF was prevented by wortmannin. Furthermore, stable C6 clones over-expressing the dominant-negative form the regulatory subunit of PI 3-kinase potentiated the expression of MMP-9 induced by IL-1 or TNF-alpha. Taken together, these results suggest that PI 3-kinase may act as a negative regulator of MMP-9 expression in C6 glioma cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Androstadienes / pharmacology
  • Animals
  • Cytokines / metabolism
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / pharmacology
  • Gene Expression Regulation, Enzymologic
  • Genes, Dominant
  • Interleukin-1 / metabolism
  • Matrix Metalloproteinase 9 / biosynthesis*
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Platelet-Derived Growth Factor / metabolism*
  • Promoter Regions, Genetic
  • RNA / metabolism
  • Rats
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction
  • Time Factors
  • Transfection
  • Tumor Cells, Cultured
  • Tumor Necrosis Factor-alpha / metabolism
  • Wortmannin


  • Androstadienes
  • Cytokines
  • Enzyme Inhibitors
  • Interleukin-1
  • Platelet-Derived Growth Factor
  • Tumor Necrosis Factor-alpha
  • RNA
  • Phosphatidylinositol 3-Kinases
  • Matrix Metalloproteinase 9
  • Wortmannin