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

Abstract

To examine the effect and underlying mechanism of action of the proteasome inhibitor lactacystin on glioma, in vitro and in vivo. 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. 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. The effects of lactacystin are associated with apoptosis induction. Proteasome inhibition may represent an effective treatment option for glioma.