Metformin inhibits glioma cell U251 invasion by downregulation of fibulin-3

Neuroreport. 2013 Jul 10;24(10):504-8. doi: 10.1097/WNR.0b013e32836277fb.

Abstract

Fibulin-3 has been considered as a regulator of glioma cell invasion, but little is known about the molecules regulating fibulin-3 expression. Metformin, an oral antidiabetic drug in the biguanide class, is known to inhibit proliferation and metastasis in a variety of cancer cells. In the present study, we determined the effect of metformin on the expression of fibulin-3 in U251 Human glioma cells. Metformin potently suppressed U251 cell adhesion and invasion. Metformin inhibited the expression of fibulin-3 at the transcriptional level. Moreover, metformin abolished the protein expression of fibulin-3 in a concentration-dependent manner. Furthermore, this compound suppressed the expression of matrix metalloproteinase-2, a key effector of glioma cell invasion, regulated by fibulin-3. Taken together, our results suggest that metformin abolishes fibulin-3 expression and subsequently inhibits invasion of glioma cells.

MeSH terms

  • Actins / biosynthesis
  • Actins / genetics
  • Blotting, Western
  • Brain Neoplasms / pathology*
  • Cell Adhesion / drug effects
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Survival / drug effects
  • Down-Regulation / drug effects
  • Down-Regulation / genetics
  • Extracellular Matrix Proteins / biosynthesis*
  • Extracellular Matrix Proteins / genetics
  • Glioma / pathology*
  • Humans
  • Hypoglycemic Agents / pharmacology*
  • Matrix Metalloproteinase 2 / biosynthesis
  • Matrix Metalloproteinase 2 / genetics
  • Metformin / pharmacology*
  • Real-Time Polymerase Chain Reaction

Substances

  • Actins
  • EFEMP1 protein, human
  • Extracellular Matrix Proteins
  • Hypoglycemic Agents
  • Metformin
  • Matrix Metalloproteinase 2