Laboratory of Veterinary Internal Medicine, College of Veterinary Medicine, Seoul National University, Seoul, Republic of Korea.
Laboratory Animal Center, CHA University, CHA Biocomplex, Seongnam, Republic of Korea.
Vet Comp Oncol. 2020 Jun;18(2):152-160. doi: 10.1111/vco.12540. Epub 2019 Oct 21.
Paclitaxel, a member of the taxane family, exhibits antitumour effects by targeting the microtubules in cancer cells. Recently, oral paclitaxel has been developed to overcome the side effects of intravenous paclitaxel administration in human patients. The objective of this study was to investigate the antitumour effects of oral paclitaxel in vitro and in vivo. Three weeks after inoculation, oral paclitaxel (25 and 50 mg/kg) or saline was administered every week for three consecutive weeks. To explore the underlying mechanism, tumour angiogenesis was examined by immunohistochemistry with an anti-CD31 antibody. Tumour cell apoptosis was detected by Terminal deoxynucleotidyl transferase dUTP Nick-End Labeling assay, and cell cycle arrest was confirmed by western blot analysis. Oral paclitaxel treatment of canine melanoma cells exerted mediated antiproliferative effects and mediated cell cycle arrest in vitro. In animal experiments, after oral paclitaxel administration, the average tumour size decreased to approximately 30% of that in the control. Histologically, oral paclitaxel showed anti-angiogenic effects and induced the apoptosis in tumour tissues. Oral paclitaxel also downregulated the intratumoural expression of cyclin D1 and inhibited cell proliferation. The study findings support potential application of oral paclitaxel as a novel chemotherapeutic strategy to treat canine melanoma. This is the first study to investigate the potential of oral paclitaxel as a therapeutic drug against canine tumours.
紫杉醇是紫杉烷类家族的成员，通过靶向癌细胞中的微管发挥抗肿瘤作用。最近，开发了口服紫杉醇以克服人类患者静脉内紫杉醇给药的副作用。本研究的目的是研究口服紫杉醇在体外和体内的抗肿瘤作用。接种后 3 周，每周连续 3 周给予口服紫杉醇（25 和 50mg/kg）或生理盐水。为了探讨潜在的机制，用抗 CD31 抗体通过免疫组织化学检查肿瘤血管生成。通过末端脱氧核苷酸转移酶 dUTP 缺口末端标记测定法检测肿瘤细胞凋亡，并通过 Western blot 分析确认细胞周期停滞。口服紫杉醇处理犬黑色素瘤细胞在体外发挥介导的增殖抑制作用和介导的细胞周期停滞。在动物实验中，口服紫杉醇给药后，平均肿瘤大小降至对照组的约 30%。组织学上，口服紫杉醇显示出抗血管生成作用，并诱导肿瘤组织中的细胞凋亡。口服紫杉醇还下调了肿瘤内 cyclin D1 的表达并抑制了细胞增殖。研究结果支持将口服紫杉醇作为一种新型化疗策略用于治疗犬黑色素瘤的潜在应用。这是第一项研究口服紫杉醇作为治疗犬肿瘤的治疗药物的潜力。
