[Role of Rac1 in the SDF-1-induced migration and invasion of human glioma cell line U251]

Zhonghua Yi Xue Za Zhi. 2012 Mar 20;92(11):727-30.
[Article in Chinese]

Abstract

Objective: To explore the role of Rac1 in the SDF-1-induced migration and invasion of glioma cells with a specific Rac1 inhibitor.

Methods: Human glioma cell lines U251 treated with SDF-1 or/and specific Rac1 inhibitor were used. The migration and invasion capacities of cells in 2D cell migration/3D invasion assay were assessed. Western blot was employed to detect the levels of Rac1 and GAPDH in cell lysates and the Rac1 activity measured by Rac1 activation assays. Immunofluorescence was used to identify the expression and intracellular location of Rac1 in U251 cells.

Results: SDF-1 significantly increased the migration and invasion capacities of U251 cells (P < 0.05). The stimulation of SDF-1 boosted the activity of Rac1 versus the unstimulated cells (P < 0.05). And Rac1 was recruited to protruding edge in SDF-1-stimulated cells. Inhibition of Rac1 with specific Rac1 inhibitor decreased the migration and invasion capacities of SDF-1-induced U251 cells (P < 0.05). In comparison with the SDF-1 treated group, the activity of Rac1 significantly decreased (P < 0.05) and the recruitment of Rac1 to protruding edge significantly decreased in the NSC23766 pre-treated group.

Conclusions: This study provides novel evidence that Rac1 modulates the SDF-1-induced migration and invasion of glioma cells. It suggests that the inhibition of Rac1 activation may be a new therapeutic target for glioma.

Publication types

  • English Abstract
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Brain Neoplasms / metabolism
  • Brain Neoplasms / pathology*
  • Cell Line, Tumor
  • Cell Movement
  • Chemokine CXCL12 / metabolism
  • Gene Expression Regulation, Neoplastic
  • Glioma / metabolism
  • Glioma / pathology*
  • Humans
  • Neoplasm Invasiveness
  • rac1 GTP-Binding Protein / metabolism*

Substances

  • CXCL12 protein, human
  • Chemokine CXCL12
  • RAC1 protein, human
  • rac1 GTP-Binding Protein