Effects of trastuzumab emtansine on canine urothelial carcinoma cells in vitro and in vivo.

IF 2.3 2区 农林科学 Q1 VETERINARY SCIENCES
Veterinary and comparative oncology Pub Date : 2024-06-01 Epub Date: 2024-03-19 DOI:10.1111/vco.12970
Kosei Sakai, Daiki Kato, Junka Yoshinaka, Yosuke Takahashi, Namiko Ikeda, Susumu Aoki, Takaaki Iguchi, Shingo Ishikawa, Norio Yamagishi, Shunsuke Shimamura, Takayuki Nakagawa
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引用次数: 0

Abstract

Urothelial carcinoma (UC) is the most common malignancy of the urinary tract in dogs and has aggressive behaviour. Although human epidermal growth factor receptor 2 (HER2) is a known therapeutic target with evidence in canine UC, the efficacy of anti-HER2 antibody drugs remains unknown. This study aimed to investigate the effects of anti-HER2 antibody drugs including trastuzumab and trastuzumab emtansine (T-DM1) on canine UC cell lines in vitro and in vivo. Four canine UC cell lines (Nene, TCCUB, Love, and Sora) were used. In western blotting, HER2 protein expression was observed in all the cell lines. Although both trastuzumab and T-DM1 showed dose-dependent growth inhibitory activity in the cell lines, T-DM1 showed much stronger activity than that of trastuzumab. In flow cytometry analyses with the canine UC cell line (Sora), T-DM1 but not trastuzumab significantly increased the percentages of early and late apoptotic cells in annexin V apoptotic assays and the sub-G1 phase fraction in cell cycle analyses. For the in vivo experiment, the canine UC cells (Sora) were subcutaneously injected into nude mice. Four days after inoculation, trastuzumab, T-DM1, or vehicle was administered intraperitoneally once a week for three times. Tumour volumes were significantly smaller in the T-DM1 group compared to the trastuzumab and vehicle control groups. These findings indicate that T-DM1 exerts a stronger antitumour effect than that of trastuzumab on canine UC cells in vitro and in vivo, possibly by inducing apoptosis due to DM1.

trastuzumab emtansine 对犬尿路上皮癌细胞在体外和体内的影响。
尿路上皮癌(UC)是犬泌尿道最常见的恶性肿瘤,具有侵袭性。虽然人类表皮生长因子受体 2(HER2)是已知的治疗靶点,在犬尿道癌中也有证据,但抗 HER2 抗体药物的疗效仍不清楚。本研究旨在探讨抗HER2抗体药物(包括曲妥珠单抗和曲妥珠单抗埃坦新(T-DM1))在体外和体内对犬UC细胞系的影响。研究使用了四种犬 UC 细胞系(Nene、TCCUB、Love 和 Sora)。在 Western 印迹中,所有细胞系都观察到了 HER2 蛋白的表达。尽管曲妥珠单抗和 T-DM1 对细胞株都表现出剂量依赖性的生长抑制活性,但 T-DM1 比曲妥珠单抗表现出更强的活性。在犬 UC 细胞系(Sora)的流式细胞术分析中,T-DM1 而不是曲妥珠单抗能显著增加附件素 V 凋亡检测中早期和晚期凋亡细胞的百分比,以及细胞周期分析中的亚 G1 期部分。在体内实验中,将犬 UC 细胞(Sora)皮下注射到裸鼠体内。接种四天后,腹腔注射曲妥珠单抗、T-DM1 或药物,每周一次,共注射三次。与曲妥珠单抗和药物对照组相比,T-DM1 组的肿瘤体积明显较小。这些研究结果表明,在体外和体内,T-DM1对犬UC细胞的抗肿瘤作用比曲妥珠单抗更强,这可能是由于DM1诱导了细胞凋亡。
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来源期刊
Veterinary and comparative oncology
Veterinary and comparative oncology 农林科学-兽医学
CiteScore
4.80
自引率
9.50%
发文量
75
审稿时长
>24 weeks
期刊介绍: Veterinary and Comparative Oncology (VCO) is an international, peer-reviewed journal integrating clinical and scientific information from a variety of related disciplines and from worldwide sources for all veterinary oncologists and cancer researchers concerned with aetiology, diagnosis and clinical course of cancer in domestic animals and its prevention. With the ultimate aim of diminishing suffering from cancer, the journal supports the transfer of knowledge in all aspects of veterinary oncology, from the application of new laboratory technology to cancer prevention, early detection, diagnosis and therapy. In addition to original articles, the journal publishes solicited editorials, review articles, commentary, correspondence and abstracts from the published literature. Accordingly, studies describing laboratory work performed exclusively in purpose-bred domestic animals (e.g. dogs, cats, horses) will not be considered.
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