Department of Clinical Studies, Ontario Veterinary College, University of Guelph, Guelph, Ontario, Canada.
Department of Clinical Sciences, College of Veterinary Medicine, Kansas State University, Manhattan, Kansas, United States of America.
PLoS One. 2021 Aug 5;16(8):e0255591. doi: 10.1371/journal.pone.0255591. eCollection 2021.
Canine urothelial carcinoma is the most common form of canine bladder cancer. Treatment with chemotherapy has variable response rates leading to most dogs succumbing to their disease within a year. Cannabidiol is an emerging treatment within the field of oncology. In reported in vivo studies, cannabidiol has induced apoptosis, reduced cell migration, and acted as a chemotherapy sensitizer in various human tumor types. The aim of this study was to characterize the effects of cannabidiol on canine urothelial carcinoma cell viability and apoptosis as both a single agent and in combination with chemotherapy in vitro.
Cannabidiol reduced cell viability and induced apoptosis in canine urothelial cells as determined by crystal violet viability assay and annexin V/propidium iodide flow cytometry. Furthermore, combinations of cannabidiol with mitoxantrone and vinblastine chemotherapy yielded significantly reduced cell viability and increased apoptosis compared to single agent treatment alone. The drug interactions were deemed synergistic based on combination index calculations. Conversely, the combination of cannabidiol and carboplatin did not result in decreased cell viability and increased apoptosis compared to single agent treatment. Combination index calculations suggested an antagonistic interaction between these drugs. Finally, the combination of the non-steroidal anti-inflammatory drug piroxicam with cannabidiol did not significantly affect cell viability, although, some cell lines demonstrated decreased cell viability when mitoxantrone was combined with piroxicam.
Cannabidiol showed promising results as a single agent or in combination with mitoxantrone and vinblastine for treatment of canine urothelial carcinoma cells. Further studies are justified to investigate whether these results are translatable in vivo.
犬尿路上皮癌是犬膀胱癌中最常见的形式。化疗的治疗效果反应率各不相同，导致大多数狗在一年内死于该病。大麻二酚是肿瘤学领域的一种新兴治疗方法。在报告的体内研究中，大麻二酚在各种人类肿瘤类型中诱导细胞凋亡、减少细胞迁移，并作为化疗增敏剂。本研究的目的是描述大麻二酚对犬尿路上皮癌细胞活力和细胞凋亡的影响，作为单一药物以及与体外化疗联合使用。
通过结晶紫活力测定法和 Annexin V/碘化丙啶流式细胞术，大麻二酚降低了犬尿路上皮细胞的活力并诱导了细胞凋亡。此外，与单一药物治疗相比，大麻二酚与米托蒽醌和长春碱化疗药物联合使用导致细胞活力显著降低和细胞凋亡增加。基于组合指数计算，药物相互作用被认为是协同的。相反，与单一药物治疗相比，大麻二酚与卡铂联合使用并未导致细胞活力降低和细胞凋亡增加。组合指数计算表明这些药物之间存在拮抗相互作用。最后，非甾体抗炎药吡罗昔康与大麻二酚联合使用并未显著影响细胞活力，尽管一些细胞系在米托蒽醌与吡罗昔康联合使用时显示出细胞活力降低。
大麻二酚作为单一药物或与米托蒽醌和长春碱联合使用，对犬尿路上皮癌细胞显示出良好的疗效。有理由进一步研究这些结果是否在体内具有可转移性。
