Inhibition of N-acetylglucosaminyltransferase V enhances sensitivity of radiotherapy in human prostate cancer

Biochem Biophys Res Commun. 2014 Aug 29;451(3):345-51. doi: 10.1016/j.bbrc.2014.06.097. Epub 2014 Aug 10.

Abstract

The purpose of this study was to investigate the relationship between N-acetylglucosaminyltransferase V (GnT-V) and radiation sensitivity of prostate cancer (PCa) cells both in vitro and in vivo. Firstly, the GnT-V expression was studied in 84 cases of PCa tissues, in which higher level of GnT-V was detected more frequently in the advanced tumors. Secondly, the GnT-V stably suppressed cell lines PCa/1079 (Lncap/1079 and PC3/1079) were constructed from PCa cell lines (Lncap and PC3) in vitro. Attenuation of GnT-V inhibited cell proliferation, migration and increased apoptosis, which resulted in enhanced radiation sensitivity of PCa cells. The underlying mechanism may be relevant to the increasing ratio of Bax/Bcl-2, the blocking transcription of NF-κB and the reduction of cell cycle G2-M arrest. Finally, in in vivo study, compared with control groups, the irradiated PCa xenograft nude mice of PCa/1079 indicated to reduce tumor-growth rate and enhance survival time. Summary, our studies showed that inhibition of GnT-V probably improved PCa cells' radiation sensitivity.

Keywords: Apoptosis; N-acetylglucosaminyltransferases V; Prostate cancer; Radiation sensitivity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / radiation effects
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Down-Regulation
  • Humans
  • Male
  • Mice
  • Mice, Nude
  • N-Acetylglucosaminyltransferases / antagonists & inhibitors*
  • N-Acetylglucosaminyltransferases / biosynthesis
  • Prostatic Neoplasms / radiotherapy*
  • Radiation Tolerance / drug effects*
  • Radiation Tolerance / genetics

Substances

  • N-Acetylglucosaminyltransferases
  • alpha-1,6-mannosylglycoprotein beta 1,6-N-acetylglucosaminyltransferase