The proteasome inhibitor lactacystin exerts its therapeutic effects on glioma via apoptosis: an in vitro and in vivo study

J Int Med Res. 2013 Feb;41(1):72-81. doi: 10.1177/0300060513476992. Epub 2013 Jan 24.


Objective: To examine the effect and underlying mechanism of action of the proteasome inhibitor lactacystin on glioma, in vitro and in vivo.

Methods: Rat C6 glioma cells were cultured with or without lactacystin. Cell proliferation, apoptosis and mitochondrial membrane potential were determined. A glioma xenograft model was established in mice and animals were treated with 0, 1 or 5 µg/20 g body weight lactacystin for 7 days. Animals were sacrificed on day 17 after completion of treatment. Apoptosis in tumour tissue was examined by terminal deoxynucleotidyl transferase dUTP nick end labeling staining. Levels of B cell lymphoma 2 (Bcl-2), and Bcl2-associated X protein (Bax) protein and mRNA, were determined in C6 cells and tumour tissues.

Results: Lactacystin significantly inhibited the proliferation of C6 cells, increased apoptosis and reduced mitochondrial membrane potential in vitro, and suppressed tumour growth in vivo. Lactacystin increased the ratio of Bax to Bcl-2 at the mRNA and protein levels, both in vitro and in vivo.

Conclusions: The effects of lactacystin are associated with apoptosis induction. Proteasome inhibition may represent an effective treatment option for glioma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcysteine / analogs & derivatives*
  • Acetylcysteine / pharmacology
  • Acetylcysteine / therapeutic use
  • Animals
  • Apoptosis / drug effects*
  • Apoptosis / genetics
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / genetics
  • Brain Neoplasms / pathology*
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Gene Expression Regulation, Neoplastic / drug effects
  • Glioma / drug therapy*
  • Glioma / genetics
  • Glioma / pathology*
  • Membrane Potential, Mitochondrial / drug effects
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Proteasome Inhibitors / pharmacology
  • Proteasome Inhibitors / therapeutic use*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Tumor Burden / drug effects
  • Xenograft Model Antitumor Assays
  • bcl-2-Associated X Protein / genetics
  • bcl-2-Associated X Protein / metabolism


  • Proteasome Inhibitors
  • RNA, Messenger
  • bcl-2-Associated X Protein
  • lactacystin
  • Acetylcysteine