Combination effect of Exportin 1 inhibitor (KPT-335) with doxorubicin or vincristine in canine lymphoma cell lines.

Abstract

Canine lymphoma is a common hematopoietic malignancy with limited therapeutic options, particularly in drug-resistant cases. Overexpression of Exportin 1 (XPO1) promotes oncogenesis by impairing the nuclear-cytoplasmic translocation of tumor suppressor proteins (TSPs). KPT-335 (Verdinexor), a selective XPO1 inhibitor, restores TSP function, inducing cell cycle arrest and apoptosis. In this study, we investigated the in vitro effects of KPT-335 alone and in combination with doxorubicin or vincristine in four canine lymphoma cell lines. KPT-335 reduced XPO1 protein expression in a dose-dependent manner, an effect reversed by proteasome inhibition, suggesting proteasome-mediated degradation. Combination treatments significantly suppressed cell proliferation compared with single agents. These findings highlight the preclinical evidence of combining KPT-335 with conventional chemotherapies in canine lymphoma.