Anti-tumor effect of proteasome inhibitor on canine urothelial carcinoma

Abstract

Canine urothelial carcinoma (cUC) is one of the most malignant tumors affecting dogs; however, its proliferative mechanism is yet to be fully elucidated. The ubiquitin-proteasome system (UPS) is an important metabolic pathway regulating protein degradation, and its dysfunction leads to apoptosis. We investigated the antitumor effect of the proteasome inhibitor bortezomib, which blocks the UPS. Bortezomib inhibited cell growth in cUC cell lines by inducing apoptosis in vitro. These findings suggest the potential of bortezomib as a novel therapeutic drug for dogs with cUC.

Keywords: bortezomib; canine urothelial carcinoma; dog; proteasome inhibitor; tumor.

Fig. 1.

Growth inhibition of Bortezomib on 8 canine urothelial carcinoma (cUC) cell lines. Dose-response curves of bortezomib in cUC cell lines. The cells were then exposed to bortezomib for 48 hr. Values are shown as the mean ± SD.

Fig. 2.

Representative images of flow cytometry. Representative data of cell cycle analysis (A) and apoptosis analysis (B). The proportions of each cell cycle phase excluding sub-G1 phase (C).

Fig. 3.

Flow-cytometry analysis of 3 canine urothelial carcinoma (cUC) cell lines treated with Bortezomib. Cells were exposed to bortezomib for 24 hr and stained with propidium iodide alone in a cell cycle assay (A) or with annexin V and propidium iodide in an apoptosis assay (B). The proportion of each phase was determined using FlowJo software. Each bar represents the mean ± SD. ***P<0.001.