Abstract
Pardaxin is an antimicrobial peptide of 33 amino acids, originally isolated from marine fish. We previously demonstrated that pardaxin has anti-tumor activity against murine fibrosarcoma, both in vitro and in vivo. In this study, we examined the anti-tumor activity, toxicity profile, and maximally-tolerated dose of pardaxin treatment in dogs with different types of refractory tumor. Local injection of pardaxin resulted in a significant reduction of perianal gland adenoma growth between 28 and 38 days post-treatment. Surgical resection of canine histiocytomas revealed large areas of ulceration, suggesting that pardaxin acts like a lytic peptide. Pardaxin treatment was not associated with significant variations in blood biochemical parameters or secretion of immune-related proteins. Our findings indicate that pardaxin has strong therapeutic potential for treating perianal gland adenomas in dogs. These data justify the veterinary application of pardaxin, and also provide invaluable information for veterinary medicine and future human clinical trials.
Highlights
For several years, nude mice have been used as in vivo experimental models to study the effects of anticancer agents
We previously reported that intratumoral injection of certain antimicrobial peptides (AMPs) induces anti-tumor responses [10, 11]
We evaluated the efficacy of pardaxin as an anticancer drug in vivo in a total of 14 dogs with naturallyoccurring cancer
Summary
Nude mice have been used as in vivo experimental models to study the effects of anticancer agents. Working with nude mice allows fine control of the experimental conditions in vivo, and the resulting findings are reliable and reproducible. The oncogenic processes in transplanted cancer cells in mouse models and naturally-occurring cancers in humans are not the same, and differences in tumor development and responses are observed [1]. Several investigations have developed novel treatment options for cancer (including urinary bladder cancer [5], canine osteosarcoma [6], B-cell lymphoma [7], prostatic hyperplasia [8], and solid tumor [9]) using dogs as models, emphasizing the importance of studying naturallyoccurring cancers in dogs for gaining insights into the biology of human cancer
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