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

Anticancer Res. 2015 Sep;35(9):4749-56.

Abstract

Background: Canine melanoma is the most common type of tumor in dogs. We investigated the effects of canine interferon-beta (cIFN-β)-overexpressing adipose tissue-derived mesenchymal stem cells (cATMSCs) on apoptosis and proliferation of canine melanoma cells.

Materials and methods: Expression of IFN-β 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 G0/G1 phases were observed in parallel with decreased cyclin D1 expression in LMeC cells treated with cIFN-β-cATMSC-conditioned media. Protein expression of active forms of caspase 3 and Bak increased in response to treatment with cIFN-β-cATMSC-conditioned media.

Conclusion: IFN-β overexpression by cATMSCs was associated with pro-apoptotic and growth-inhibitory effects on canine melanoma cells. The antitumor effects of these cells have therapeutic potential for the treatment of canine melanoma.

Keywords: Melanoma; apoptosis; cell cycle; interferon β; mesenchymal stem cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / cytology*
  • Animals
  • Apoptosis* / drug effects
  • Caspase 3 / metabolism
  • Cell Cycle Checkpoints / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Culture Media, Conditioned / pharmacology
  • Dogs
  • Enzyme Activation / drug effects
  • Interferon-beta / metabolism*
  • Melanoma / pathology*
  • Mesenchymal Stem Cells / drug effects
  • Mesenchymal Stem Cells / metabolism*
  • bcl-2 Homologous Antagonist-Killer Protein / metabolism

Substances

  • Culture Media, Conditioned
  • bcl-2 Homologous Antagonist-Killer Protein
  • Interferon-beta
  • Caspase 3