Silencing of HIF-1α enhances the radiation sensitivity of human glioma growth in vitro and in vivo

Neuropharmacology. 2015 Feb:89:168-74. doi: 10.1016/j.neuropharm.2014.05.009. Epub 2014 May 20.

Abstract

Gliomas are the leading cause of cancer-related mortality worldwide, and the incidence is increasing. Because gliomas often become resistant to radiation treatment, it is urgent to develop novel therapeutic methods that are more effective and less toxic than current therapies so as to enhance patient survival and quality of life. Effective enhancement of radiation therapy for gliomas in vivo and in vitro was observed upon silencing of hypoxia-inducible factor 1α (HIF-1α) with RNA interference; this enhancement was related to changes in the cell cycle and apoptosis that were accompanied by modulation of Cdc2, cyclin B1, and Bcl-2 expression. Our data suggest that HIF-1α silencing combined with radiation therapy will increase the therapeutic efficacy of glioma treatment via regulation of cell cycle and apoptosis-related signaling pathways.

Keywords: Gliomas; HIF-1α; Pathway; RNAi; Radiation sensitivity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain Neoplasms / genetics
  • Brain Neoplasms / metabolism*
  • Brain Neoplasms / radiotherapy
  • Cell Line, Tumor
  • Female
  • Gene Silencing / physiology*
  • Glioma / genetics
  • Glioma / metabolism*
  • Glioma / radiotherapy
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / deficiency*
  • Hypoxia-Inducible Factor 1, alpha Subunit / genetics
  • Mice
  • Mice, Nude
  • Radiation Tolerance / physiology*
  • Xenograft Model Antitumor Assays / methods

Substances

  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit