Shiomitsu K, Sajo E, Rubin C, Sehgal I
Department of Veterinary Clinical Sciences, Cancer Treatment Unit, Louisiana State University, Baton Rouge, LA, USA.
Department of Physics, Medical Physics Program, University of Massachusetts Lowell, Lowell, MA, USA.
Vet Comp Oncol. 2016 Mar;14(1):13-27. doi: 10.1111/vco.12046. Epub 2013 Jun 13.
ENMD-2076 is an aurora kinase inhibitor that also has multi-target tyrosine kinase inhibitor properties. In this study, the mRNA and the protein expression of aurora-A and aurora-B were evaluated in three canine mast cell tumour cell lines. Dose-dependent cytotoxicity was seen in the cells treated, and it affected the cell cycle with cells in the G2/M phase being selectively killed. The cells were also evaluated for radiosensitivity with/without ENMD-2076, and radiosensitization was seen after 3 Gy and 6 Gy exposures with ENMD-2076 for 48 h. Protein expression of caspase-3 was gradually increased, and the expression intensity was highest at 24 h post irradiation in cells without ENMD-2076 treatment, which indicates that radiation exposure with ENMD-2076-induced cell death faster than radiation treatment alone. Our study results suggest the potential usefulness of treating canine mast cell tumours with aurora kinase inhibitors alone or in conjunction with radiation therapy.
ENMD - 2076是一种极光激酶抑制剂，同时还具有多靶点酪氨酸激酶抑制剂的特性。在本研究中，对三种犬肥大细胞瘤细胞系中极光A和极光B的mRNA及蛋白表达进行了评估。在接受处理的细胞中观察到剂量依赖性细胞毒性，其影响细胞周期，选择性杀死处于G2/M期的细胞。还对细胞在有/无ENMD - 2076情况下的放射敏感性进行了评估，在使用ENMD - 2076处理48小时后，3 Gy和6 Gy照射剂量下均出现了放射增敏作用。在未用ENMD - 2076处理的细胞中，半胱天冬酶 - 3的蛋白表达逐渐增加，且在照射后24小时表达强度最高，这表明联合使用ENMD - 2076进行辐射比单独进行辐射诱导细胞死亡更快。我们的研究结果表明，单独使用极光激酶抑制剂或与放射治疗联合用于治疗犬肥大细胞瘤具有潜在的有效性。
