RESUMO
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.
Assuntos
Antineoplásicos , Apoptose , Bortezomib , Doenças do Cão , Inibidores de Proteassoma , Neoplasias da Bexiga Urinária , Animais , Cães , Bortezomib/farmacologia , Bortezomib/uso terapêutico , Inibidores de Proteassoma/farmacologia , Inibidores de Proteassoma/uso terapêutico , Doenças do Cão/tratamento farmacológico , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Apoptose/efeitos dos fármacos , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/veterinária , Carcinoma de Células de Transição/tratamento farmacológico , Carcinoma de Células de Transição/veterináriaRESUMO
Podoplanin (PDPN) is a prognostic factor and is involved in several mechanisms of tumor progression in human squamous cell carcinoma (SCC). Canine non-tonsillar SCC (NTSCC) is a common oral tumor in dogs and has a highly invasive characteristic. In this study, we investigated the function of PDPN in canine NTSCC. In canine NTSCC clinical samples, PDPN overexpression was observed in 80% of dogs with NTSCC, and PDPN expression was related to ki67 expression. In PDPN knocked-out canine NTSCC cells, cell proliferation, cancer stemness, and migration were suppressed. As the mechanism of PDPN-mediated cell proliferation, PDPN knocked-out induced apoptosis and G2/M cell cycle arrest in canine NTSCC cells. These findings suggest that PDPN promotes tumor malignancies and may be a novel biomarker and therapeutic target for canine NTSCC.