Cabazitaxel Demonstrates Potent Antitumour Activity Against Canine Large-Cell Alimentary Lymphoma In Vitro and In Vivo.

Canine large-cell alimentary lymphoma (LCAL) is an aggressive malignancy with limited effective treatment options and a poor prognosis. In a preliminary drug screening study using three canine LCAL cell lines (CLC, Ema, and Nody-1), the taxane cabazitaxel (CBZ) was identified as a promising candidate drug. This study aimed to evaluate the antitumour effects of CBZ in vitro and in vivo and determine its potential as a novel therapeutic candidate for canine LCAL. Cell viability, tubulin polymerisation, cell cycle distribution, and apoptosis were assessed in CLC, Ema, and Nody-1 cells following treatment with CBZ or vehicle control. In addition, the effect of CBZ was evaluated in a xenotransplantation mouse model established using CLC cells. CBZ reduced cell viability across all cell lines in a dose-dependent manner, with sub-nanomolar half-maximal inhibitory concentrations. A tubulin polymerisation assay demonstrated that CBZ increased polymerised tubulin levels, indicating microtubule stabilisation. CBZ treatment induced G2/M cell cycle arrest and significantly increased apoptotic cell populations, accompanied by decreased procaspase-3 levels and increased cleaved caspase-3 expression. In vivo, CBZ treatment reduced ascites accumulation and significantly prolonged survival relative to the vehicle control. These findings suggest that CBZ induces G2/M cell cycle arrest and caspase-dependent apoptosis through tubulin stabilisation and suppresses tumour progression in vivo. CBZ represents a promising therapeutic candidate for canine LCAL.