Flint Animal Cancer Center, Colorado State University, 300 West Drake Road, Fort Collins, Colorado 80523, USA.
Can J Vet Res. 2020 Apr;84(2):115-123.
The objective of this study was to evaluate taurolidine as a therapy for transitional cell carcinomas in canine patients. Transitional cell carcinoma (TCC) is the most common cancer of the urinary bladder in dogs and accounts for approximately 2% of reported malignancies in this species. There is no cure for this neoplasm and most dogs are lost from complications associated with progression of the local disease. Taurolidine has been shown to have anti-tumor and antiangiogenic effects against a variety of neoplasms in human and animal models. Four canine TCC cell lines were treated with various concentrations of taurolidine, mitoxantrone, and piroxicam alone. In addition, combinations of taurolidine/mitoxantrone, taurolidine/piroxicam, mitoxantrone/piroxicam, and taurolidine/mitoxantrone/piroxicam were assessed. Susceptibility of the TCC cell lines was based on a 72-hour growth inhibition assay using resazurin with absorbance measured at λ530/590. The ability of taurolidine to induce apoptosis was evaluated on 2 of the cell lines with an Annexin-V/propidium iodide assay. All cell lines were susceptible to treatment with taurolidine, mitoxantrone, and piroxicam alone. The results of the combination therapies of the 3 drugs were dependent on cell line and concentration and revealed no change in cell growth inhibition, a subadditive relationship, or a synergistic relationship. Taurolidine induced apoptosis in a concentration- and time-dependent fashion. Taurolidine alone showed significant effects on cell viability in canine TCC cell lines and these effects can be potentially enhanced with the addition of mitoxantrone and/or piroxicam.
本研究旨在评估牛磺罗定作为犬患移行细胞癌的治疗方法。移行细胞癌（TCC）是犬膀胱最常见的癌症，约占该物种报告的恶性肿瘤的 2%。这种肿瘤没有治愈方法，大多数犬因局部疾病进展相关并发症而死亡。牛磺罗定已被证明对人类和动物模型中的多种肿瘤具有抗肿瘤和抗血管生成作用。将四种犬 TCC 细胞系用不同浓度的牛磺罗定、米托蒽醌和吡罗昔康单独处理。此外，还评估了牛磺罗定/米托蒽醌、牛磺罗定/吡罗昔康、米托蒽醌/吡罗昔康和牛磺罗定/米托蒽醌/吡罗昔康的组合。TCC 细胞系的敏感性基于使用 Resazurin 的 72 小时生长抑制测定，并用 λ530/590 测量吸光度。用 Annexin-V/碘化丙啶测定法评估牛磺罗定在 2 个细胞系中诱导细胞凋亡的能力。所有细胞系均对牛磺罗定、米托蒽醌和吡罗昔康单独治疗敏感。3 种药物联合治疗的结果取决于细胞系和浓度，并且未显示细胞生长抑制、次加性或协同关系的变化。牛磺罗定以浓度和时间依赖性方式诱导细胞凋亡。牛磺罗定单独对犬 TCC 细胞系的细胞活力有显著影响，并且这些影响可通过添加米托蒽醌和/或吡罗昔康来增强。
