Therapeutic potential of bleomycin plus suicide or interferon-β gene transfer combination for spontaneous feline and canine melanoma

Lucrecia Agnetti1, Chiara Fondello1, Marcela S. Villaverde1, Gerardo C. Glikin1, Liliana M.E. Finocchiaro1

1 Unidad de Transferencia Genética Instituto de Oncología "Ángel H. Roffo", Universidad de Buenos Aires, Buenos Aires, Argentina

Correspondence to:

Liliana M.E. Finocchiaro, email: [email protected]

Keywords: melanoma, HSV-thymidine kinase, interferon-β, bleomycin, spheroids

Received: July 11, 2017 Accepted: November 26, 2017 Published: December 28, 2017


We originated and characterized melanoma cell lines derived from tumors of two feline and two canine veterinary patients. These lines reestablished the morphology, physiology and cell heterogeneity of their respective parental tumors. We evaluated the cytotoxicity of bleomycin (BLM) alone, or combined with interferon-β (IFN-β) or HSVtk/GCV suicide gene (SG) lipofection on these cells. Although the four animals presented stage III disease (WHO system), SG treated feline tumors displayed stable disease in vivo, while the canine ones exhibited partial response. Their derived cell lines reflected this behavior. Feline were significantly more sensitive than canine cells to IFN-β gene transfer. BLM improved the antitumor effects of both genes. The higher levels of reactive oxygen species (ROS) significantly correlated with membrane and DNA damages, emphasizing ROS intervention in apoptotic and necrotic cell death. After 3 days of BLM alone or combined with gene treatments, the colony forming capacity of two canine and one feline treatments survivor cells almost disappeared. Taken together, these results suggest that the treatments eradicated tumor initiating cells and support the clinical potential of the tested combinations.

PII: 387