Introduction

Gliomas are the second most common canine primary brain tumor. These tumors are most commonly treated with radiation therapy and generally have a guarded prognosis. The role of systemic therapy in treating canine gliomas is largely unresolved; however, recent human glioma data suggest that bortezomib (BORT) (Velcade®), a proteasome inhibitor, in combination with radiation therapy may lead to an improved clinical outcome.

Methods

We identified the IC50 of BORT in two canine glioma cell lines, SDT3G and J3TBG, using an ATP-based cell viability assay. We then treated cells with two doses of BORT (50 nM and 75 nM) and assessed the effects of this treatment on apoptosis via flow cytometry.

Results

Treatment of canine glioma cells resulted in a dose-dependent decrease in cell-viability with IC50 values calculated as 45 nM (J3TBG) and 67 nM (SDT3G).

Treatment of the J3TBG cell line with BORT resulted in a decreased percentage of viable cells and an increased percentage of apoptotic cells at both 48 and 72 h. Both of these effects were statistically significant in comparison to the vehicle only (DMSO) treated cells (p<0.01). Furthermore, there was a statistically significant increase in apoptosis between the 50 nM and 75 nM doses, indicating a dose-dependent response. Similar responses were seen in the SDT3G cell line.

Experiments to assess the effect of radiation plus BORT on the clonogenic potential of canine glioma cells are ongoing.

Conclusion

BORT significantly reduces the viability of canine glioma cells via induction of apoptosis.

Funding Information

This work was funded by a Resident Research Grant from the Veterinary Cancer Society.