Exportin 1 (XPO1) Expression and Effectiveness of XPO1 Inhibitor Against Canine Lymphoma Cell Lines

Abstract

Lymphoma is the most common neoplasm of lymphoid tissues in dogs. Exportin 1 (XPO1) is an important major nuclear receptor for exporting proteins and RNA species. The XPO1 upregulation can eliminate some tumor suppressor proteins (TSPs) function upon their nuclear–cytoplasmic export. The XPO1 inhibitor, KPT-335, blocks the translocation of TSPs and restores their function to induce cell cycle arrest, apoptosis, and cell proliferation. This in vitro study aimed to evaluate the XPO1 mRNA and protein expression in canine lymphoma cell lines and confirm the relevance with KPT-335. XPO1 mRNA and protein levels were quantified, and the effect of KPT-335 was assessed by a cell proliferation assay. The results indicated that XPO1 mRNA and protein were highly expressed in 17-71, CLBL-1, CLC, CLGL-90, and UL-1, and were moderately expressed in GL-1, Ema, and Nody-1. All canine lymphoma cell lines showed dose-dependent growth inhibition and decreased cell viability in response to KPT-335, with IC50 concentrations ranged from 89.8–418 nM. The expression levels of XPO1 mRNA and protein were related; however, no correlation was found between those expression levels and the efficacy of KPT-335. These findings suggest that XPO1 may represent a promising target for therapeutic intervention in canine lymphoma.