C6 Ceramide Induces Apoptosis of Canine Oral Melanoma by Attenuating the Wnt/β-catenin Signaling

Melanoma is prevalent in canine oral tumors.C6 ceramide exerts powerful antitumor activity in multiple types of cancer in various ways.In this study, we investigated the functions of C6 ceramide in canine melanoma cells and xenograft models and elucidated its mechanism.The results showed that C6 ceramide significantly inhibits canine oral melanoma cell growth, migration, and invasion, as well as in xenograft models.Moreover, significant alterations were observed in cell cycle distribution and apoptosis.Subsequently, upregulations of caspase 8 and 3 were found, indicating that C6 ceramide activated the extrinsic apoptotic pathway.Finally, the expressions of p-GSK3βSer9 and β-Catenin were significantly reduced following C6 ceramide treatment, while no changes were observed in GSK3β.In conclusion, C6 ceramide exhibits remarkable antitumor activity by triggering the extrinsic apoptotic pathway and inactivating Wnt/β-catenin signaling in canine oral melanoma.