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

  • Yosuke Takahashi
    Veterinary Medical Centre The University of Tokyo Tokyo Japan
  • Kosei Sakai
    Laboratory of Small Animal Clinical Medicine, Graduate School of Veterinary Sciences Osaka Metropolitan University Osaka Japan
  • Norio Yamagishi
    Laboratory of Large Animal Clinical Medicine, Graduate School of Veterinary Sciences Osaka Metropolitan University Osaka Japan
  • Namiko Ikeda
    Laboratory of Veterinary Surgery, Graduate School of Agricultural and Life Sciences The University of Tokyo Tokyo Japan
  • Daiki Kato
    Laboratory of Veterinary Surgery, Graduate School of Agricultural and Life Sciences The University of Tokyo Tokyo Japan
  • Susumu Aoki
    Laboratory of Veterinary Surgery, Graduate School of Agricultural and Life Sciences The University of Tokyo Tokyo Japan
  • Junka Yoshinaka
    Laboratory of Small Animal Clinical Medicine, Graduate School of Veterinary Sciences Osaka Metropolitan University Osaka Japan
  • Takaaki Iguchi
    Laboratory of Veterinary Surgery, Graduate School of Agricultural and Life Sciences The University of Tokyo Tokyo Japan
  • Shingo Ishikawa
    Laboratory of Large Animal Clinical Medicine, Graduate School of Veterinary Sciences Osaka Metropolitan University Osaka Japan
  • Shunsuke Shimamura
    Laboratory of Small Animal Clinical Medicine, Graduate School of Veterinary Sciences Osaka Metropolitan University Osaka Japan
  • Takayuki Nakagawa
    Laboratory of Veterinary Surgery, Graduate School of Agricultural and Life Sciences The University of Tokyo Tokyo Japan

書誌事項

公開日
2024-03-19
資源種別
journal article
権利情報
  • http://creativecommons.org/licenses/by/4.0/
DOI
  • 10.1111/vco.12970
公開者
Wiley

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説明

<jats:title>Abstract</jats:title><jats:p>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.</jats:p>

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