Shoeneman J K, Ehrhart E J, Charles J B, Thamm D H
Flint Animal Cancer Center, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO, USA.
Cell and Molecular Biology Graduate Program, Colorado State University, Fort Collins, CO, USA.
Vet Comp Oncol. 2016 Jun;14(2):e45-57. doi: 10.1111/vco.12104. Epub 2014 Jun 13.
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.
犬淋巴瘤（LSA）和骨肉瘤（OS）死亡率高，仍需要更有效的治疗方法。生存素是一种凋亡抑制蛋白（IAP）家族成员，可抑制细胞凋亡并促进细胞增殖，在人类和犬类癌症中通常表达上调。生存素表达是犬LSA和OS的不良预后因素，犬LSA和OS细胞系表达高水平的生存素。在本研究中，我们证明，使用临床适用的锁核酸反义寡核苷酸（EZN-3042，美国新泽西州皮斯卡塔韦镇恩宗制药公司）下调犬LSA和OS细胞中的生存素可在体外抑制生长、诱导凋亡并增强化学敏感性，在原位犬OS异种移植中抑制生存素转录和蛋白质产生。我们的研究结果强烈表明，针对生存素的治疗可能对犬LSA和OS有效，并支持对患癌犬使用EZN-3042进行评估。
