TGF-β/Smad2/3 signal pathway involves in U251 cell proliferation and apoptosis

Gene. 2015 May 10;562(1):76-82. doi: 10.1016/j.gene.2015.02.049. Epub 2015 Feb 19.

Abstract

TGF-β/Smad2/3 signal pathway is regarded as a central regulator in various tumors, but its roles in brain cancer therapy remain unknown. In this study, we identify that the TGF-β/Smad2/3 signal pathway is activated in human brain glioma cells; inhibitor (SB203580) and siRNA against Smad2/3 quickly inhibited the phosphorylation of Smad2 and 3, expression of its major downstream gene, Ki-67, arrested cells in the G2/M phase and induced apoptosis of cells. The findings suggest that TGF-β/Smad2/3 pathway plays a key role in U251 cell growth and metastasis, which suggests its potential role in the molecular therapy of brain cancer.

Keywords: Apoptosis; Bcl-2; Caspase-3; TGF-β/Smad2/3.

MeSH terms

  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • G2 Phase Cell Cycle Checkpoints / drug effects
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Imidazoles / pharmacology
  • Ki-67 Antigen / genetics
  • Ki-67 Antigen / metabolism
  • Neuroglia / drug effects
  • Neuroglia / metabolism
  • Neuroglia / pathology
  • Phosphorylation / drug effects
  • Pyridines / pharmacology
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • Signal Transduction / genetics*
  • Smad2 Protein / antagonists & inhibitors
  • Smad2 Protein / genetics*
  • Smad2 Protein / metabolism
  • Smad3 Protein / antagonists & inhibitors
  • Smad3 Protein / genetics*
  • Smad3 Protein / metabolism
  • Transforming Growth Factor beta / genetics*
  • Transforming Growth Factor beta / metabolism

Substances

  • Imidazoles
  • Ki-67 Antigen
  • Pyridines
  • RNA, Small Interfering
  • SMAD2 protein, human
  • SMAD3 protein, human
  • Smad2 Protein
  • Smad3 Protein
  • Transforming Growth Factor beta
  • SB 203580