Ito K, Miyamoto R, Tani H, Kurita S, Kobayashi M, Tamura K, Bonkobara M
Department of Veterinary Clinical Pathology, Nippon Veterinary and Life Science University, Musashino-shi, Tokyo, Japan.
J Vet Pharmacol Ther. 2018 Feb;41(1):e45-e48. doi: 10.1111/jvp.12449. Epub 2017 Aug 17.
Canine histiocytic sarcoma (HS) is an aggressive and highly metastatic tumor. Previously, the kinase inhibitor dasatinib was shown to have potent growth inhibitory activity against HS cells in vitro, possibly via targeting the EPHA2 receptor. Here, the in vivo effect of dasatinib in HS cells was investigated using a xenograft mouse model. Moreover, the expression status of EPHA2 was examined in six HS cell lines, ranging from insensitive to highly sensitive to dasatinib. In the HS xenograft mouse model, dasatinib significantly suppressed tumor growth, as illustrated by a decrease in mitotic and Ki67 indices and an increase in apoptotic index in tumor tissues. On Western blot analysis, EPHA2 was only weakly detected in all HS cell lines, regardless of sensitivity to dasatinib. Dasatinib likely results in the inhibition of xenograft tumor growth via a mechanism other than targeting EPHA2. The findings of this study suggest that dasatinib is a targeted therapy drug worthy of further exploration for the treatment of canine HS.
犬组织细胞肉瘤（HS）是一种侵袭性强且具有高度转移性的肿瘤。此前研究表明，激酶抑制剂达沙替尼在体外对HS细胞具有强大的生长抑制活性，可能是通过靶向EPH A2受体实现的。在此，利用异种移植小鼠模型研究了达沙替尼对HS细胞的体内作用。此外，还检测了6种对达沙替尼从不敏感到高度敏感的HS细胞系中EPH A2的表达状态。在HS异种移植小鼠模型中，达沙替尼显著抑制肿瘤生长，肿瘤组织中的有丝分裂指数和Ki67指数降低，凋亡指数升高。蛋白质免疫印迹分析显示，无论对达沙替尼的敏感性如何，在所有HS细胞系中仅能微弱检测到EPH A2。达沙替尼可能通过靶向EPH A2以外的机制抑制异种移植肿瘤生长。本研究结果表明，达沙替尼是一种值得进一步探索用于治疗犬HS的靶向治疗药物。
