Pro-apoptotic and Growth-inhibitory Effect of IFN-β-Overexpressing Canine Adipose Tissue-derived Mesenchymal Stem Cells Against Melanoma Cells

Background: Canine melanoma is the most common type of tumor in dogs. We investigated the effects of canine interferon-beta (cIFN-beta)-overexpressing adipose tissue-derived mesenchymal stem cells (cATMSCs) on apoptosis and proliferation of canine melanoma cells. Materials and Methods: Expression of IFN-beta in cATMSCs was confirmed using reverse transcription-polymerase chain reaction and enzyme linked immunosorbent assays. Flow cytometry was performed for cell-cycle analysis and apoptotic cell quantification of LMeC (melanoma) cells. Protein expression of cyclin D1, procaspase-3, activated caspase-3, and Bcl-2 homologous antagonist killer (Bak) was evaluated by western blot analysis. Results: Decreased proportions of cells in S-and G(0)/G(1) phases were observed in parallel with decreased cyclin D1 expression in LMeC cells treated with cIFN-beta-cATMSC-conditioned media. Protein expression of active forms of caspase 3 and Bak increased in response to treatment with cIFN-beta-cATMSC-conditioned media. Conclusion: IFN-beta overexpression by cATMSCs was associated with proapoptotic and growth-inhibitory effects on canine melanoma cells. The antitumor effects of these cells have therapeutic potential for the treatment of canine melanoma.