Ong S M, Saeki K, Kok M K, Tanaka Y, Choisunirachon N, Yoshitake R, Nishimura R, Nakagawa T
Laboratory of Veterinary Surgery, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1, Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan.
Laboratory of Veterinary Surgery, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1, Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan.
Res Vet Sci. 2017 Aug;113:130-135. doi: 10.1016/j.rvsc.2017.09.019. Epub 2017 Sep 19.
Osteosarcoma (OSA) in dogs is locally invasive and highly malignant. Distant metastasis is the most common cause of death. To date, the survival rate in dogs with OSA remains poor. The cytotoxic effects of etoposide against canine OSA cell lines, either alone or in combination with piroxicam, have been previously demonstrated in vitro. The aim of this study was to evaluate the anti-tumour effect of etoposide alone and in combination with piroxicam on canine OSA using murine models. Etoposide single agent treatment significantly delayed tumour progression with a marked reduction in Ki-67 immunoreactivity in tumour tissue. Concomitant treatment with piroxicam did not enhance the anti-tumour efficacy of etoposide. Etoposide single agent treatment and combination treatment with piroxicam down-regulated survivin expression, but was not followed by increased apoptotic activity. These findings indicate that etoposide might be a promising novel therapeutic for canine OSA. Further investigations into its potential for clinical application in veterinary oncology are warranted.
犬骨肉瘤（OSA）具有局部侵袭性且恶性程度高。远处转移是最常见的死亡原因。迄今为止，患有OSA的犬的存活率仍然很低。依托泊苷对犬OSA细胞系的细胞毒性作用，无论是单独使用还是与吡罗昔康联合使用，此前已在体外得到证实。本研究的目的是使用小鼠模型评估依托泊苷单独以及与吡罗昔康联合使用对犬OSA的抗肿瘤作用。依托泊苷单药治疗显著延迟了肿瘤进展，肿瘤组织中Ki-67免疫反应性明显降低。吡罗昔康联合治疗并未增强依托泊苷的抗肿瘤疗效。依托泊苷单药治疗以及与吡罗昔康联合治疗下调了生存素表达，但并未伴随凋亡活性增加。这些发现表明，依托泊苷可能是一种有前景的犬OSA新型治疗药物。有必要进一步研究其在兽医肿瘤学临床应用中的潜力。
