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Effects of trastuzumab emtansine on canine urothelial carcinoma cells in vitro and in vivo.
- Source :
-
Veterinary and comparative oncology [Vet Comp Oncol] 2024 Jun; Vol. 22 (2), pp. 230-238. Date of Electronic Publication: 2024 Mar 19. - Publication Year :
- 2024
-
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.<br /> (© 2024 The Authors. Veterinary and Comparative Oncology published by John Wiley & Sons Ltd.)
- Subjects :
- Animals
Dogs
Cell Line, Tumor
Mice
Antineoplastic Agents, Immunological pharmacology
Antineoplastic Agents, Immunological therapeutic use
Maytansine pharmacology
Maytansine analogs & derivatives
Maytansine therapeutic use
Receptor, ErbB-2 metabolism
Mice, Nude
Female
Apoptosis drug effects
Antineoplastic Agents pharmacology
Antineoplastic Agents therapeutic use
Dog Diseases drug therapy
Trastuzumab pharmacology
Trastuzumab therapeutic use
Ado-Trastuzumab Emtansine pharmacology
Ado-Trastuzumab Emtansine therapeutic use
Subjects
Details
- Language :
- English
- ISSN :
- 1476-5829
- Volume :
- 22
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Veterinary and comparative oncology
- Publication Type :
- Academic Journal
- Accession number :
- 38502572
- Full Text :
- https://doi.org/10.1111/vco.12970