Knockdown of astrocyte elevated gene-1 inhibits proliferation and enhancing chemo-sensitivity to cisplatin or doxorubicin in neuroblastoma cells

J Exp Clin Cancer Res. 2009 Feb 15;28(1):19. doi: 10.1186/1756-9966-28-19.

Abstract

Background: Astrocyte elevated gene-1 (AEG-1) was originally characterized as a HIV-1-inducible gene in primary human fetal astrocyte. Recent studies highlight a potential role of AEG-1 in promoting tumor progression and metastasis. The aim of this study was to investigate if AEG-1 serves as a potential therapeutic target of human neuroblastoma.

Methods: We employed RNA interference to reduce AEG-1 expression in human neuroblastoma cell lines and analyzed their phenotypic changes.

Results: We found that the knockdown of AEG-1 expression in human neuroblastoma cells significantly inhibited cell proliferation and apoptosis. The specific downregulation induced cell arrest in the G0/G1 phase of cell cycle. In the present study, we also observed a significant enhancement of chemo-sensitivity to cisplatin and doxorubicin by knockdown of AEG-1.

Conclusion: Our study suggests that overexpressed AEG-1 enhance the tumorogenic properties of neuroblastoma cells. The inhibition of AEG-1 expression could be a new adjuvant therapy for neuroblastoma.

MeSH terms

  • Apoptosis / drug effects
  • Apoptosis / genetics
  • Cell Adhesion Molecules / antagonists & inhibitors*
  • Cell Adhesion Molecules / biosynthesis
  • Cell Adhesion Molecules / genetics
  • Cell Growth Processes / drug effects
  • Cell Growth Processes / genetics
  • Cell Line, Tumor
  • Cisplatin / pharmacology*
  • Disease Progression
  • Doxorubicin / pharmacology*
  • G1 Phase / genetics
  • Humans
  • Membrane Proteins
  • Neuroblastoma / drug therapy*
  • Neuroblastoma / genetics*
  • Neuroblastoma / metabolism
  • Neuroblastoma / pathology
  • RNA Interference
  • RNA, Small Interfering / genetics
  • RNA-Binding Proteins
  • Resting Phase, Cell Cycle / genetics
  • Transfection

Substances

  • Cell Adhesion Molecules
  • MTDH protein, human
  • Membrane Proteins
  • RNA, Small Interfering
  • RNA-Binding Proteins
  • Doxorubicin
  • Cisplatin