Canine cancers develop in immunocompetent environments and share many similar features observed in human cancers, such as long periods of latency for initiation, progression and development, metastasis, acquired drug resistance and recurrence. Osteosarcoma is a primary bone tumor that occurs in dogs. It is highly aggressive and metastatic in nature, and the therapeutic methods utilized to treat this primary canine tumor are very limited. We have successfully established canine osteosarcoma orthotopic xenograft models with NSG mice (from Jackson Lab) in vivo. Ouabain, known as Na+, K+ ATPase inhibitor, has been used for many years in human clinical applications for the treatment of congestive heart failure. Recently, ouabain has been investigated for potential anticancer properties. However, the therapeutic dose window is very narrow because the side effects of ouabain overdose can be lethal. In an attempt to mitigate such narrow therapeutic margin of safety, ouabain was formulated in lipid double emulsion by using microfluidic synthesis method or membrane emulsification method. Our preliminary results showed enhanced antitumor activities of ouabain in double emulsion or nanoemulsion against canine osteosarcoma cell lines in vitro and in orthotopic xenograft models in vivo. The safety and delivery efficiency of ouabain in vivo was also improved, suggesting a therapeutic application of ouabain double emulsion could be benefit in canine osteosarcoma targeting therapy.

Citation Format: Jun Wu, Meng-Yin Hsieh, Yan Wang, Eugene Roberts, Derek Vallejo, Abraham Lee, Richard Ermel. Antitumor properties of ouabain in lipid double emulsion in orthotopic canine osteosarcoma xenografted mouse model. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5412. doi:10.1158/1538-7445.AM2014-5412