Effect of Proteasome Inhibitors on Canine Lymphoma Cell Response to CHOP Chemotherapy In Vitro

Abstract

Canine lymphoma is commonly treated with CHOP chemotherapy. Proteasome inhibitors are employed with CHOP for the treatment of human hematological malignancies. The aim of this study was to determine the effect of proteasome inhibitors on canine B-cell lymphoma cell line (CLBL-1) cell viability, and to investigate whether proteasome inhibitors sensitize cells to CHOP agents. We hypothesized that proteasome inhibitors will reduce CLBL-1 viability and will be synergistic with CHOP compounds. CLBL-1 was sensitive to proteasome inhibition. The IC50 of bortezomib was 15.1 nM and of ixazomib was 59.14 nM. Proteasome inhibitors plus doxorubicin had a synergistic effect on CLBL-1 viability, with vincristine there were different effects depending on the combination ratio, and there was an antagonistic effect with 4-HC (cyclophosphamide). These results have clinical utility, as proteasome inhibition could potentially be used with a synergizing CHOP compound to improve responsiveness to chemotherapy for canine lymphoma patients.