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Survivin inhibition via EZN ‐3042 in canine lymphoma and osteosarcoma
Author(s) -
Shoeneman J. K.,
Ehrhart E. J.,
Charles J. B.,
Thamm D. H.
Publication year - 2016
Publication title -
veterinary and comparative oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.864
H-Index - 34
eISSN - 1476-5829
pISSN - 1476-5810
DOI - 10.1111/vco.12104
Subject(s) - survivin , canine lymphoma , apoptosis , cancer research , osteosarcoma , downregulation and upregulation , inhibitor of apoptosis , lymphoma , medicine , cell growth , cancer , biology , programmed cell death , gene , biochemistry , genetics
Canine lymphoma ( LSA ) and osteosarcoma ( OS ) have high mortality rates and remain in need of more effective therapeutic approaches. Survivin, an inhibitor of apoptosis ( IAP ) family member protein that inhibits apoptosis and drives cell proliferation, is commonly elevated in human and canine cancer. Survivin expression is a negative prognostic factor in dogs with LSA and OS , and canine LSA and OS cell lines express high levels of survivin. In this study, we demonstrate that survivin downregulation in canine LSA and OS cells using a clinically applicable locked nucleic acid antisense oligonucleotide ( EZN ‐3042, Enzon Pharmaceuticals, Piscataway Township, NJ, USA) inhibits growth, induces apoptosis and enhances chemosensitivity in vitro , and inhibits survivin transcription and protein production in orthotopic canine OS xenografts. Our findings strongly suggest that survivin‐directed therapies might be effective in treatment of canine LSA and OS and support evaluation of EZN ‐3042 in dogs with cancer.