Journal of Veterinary Science

The Korean Society of Veterinary Science (대한수의학회)
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In vitro evaluation of the antitumor activity of axitinib in canine mammary gland tumor cell lines

  • Hye-Gyu Lee (Laboratory of Veterinary Internal Medicine, Department of Veterinary Clinical Science, College of Veterinary Medicine, Seoul National University) ;
  • Ga-Hyun Lim (Laboratory of Veterinary Internal Medicine, Department of Veterinary Clinical Science, College of Veterinary Medicine, Seoul National University) ;
  • Ju-Hyun An (Department of Veterinary Emergency and Critical Care Medicine and Institute of Veterinary Science, College of Veterinary Medicine, Kangwon National University) ;
  • Su-Min Park (Haemaru Referral Animal Hospital) ;
  • Kyoung-Won Seo (Laboratory of Veterinary Internal Medicine, Department of Veterinary Clinical Science, College of Veterinary Medicine, Seoul National University) ;
  • Hwa-Young Youn (Laboratory of Veterinary Internal Medicine, Department of Veterinary Clinical Science, College of Veterinary Medicine, Seoul National University)
  • Received : 2023.07.23
  • Accepted : 2023.11.09
  • Published : 2024.01.31
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Abstract

Background: Axitinib, a potent and selective inhibitor of vascular endothelial growth factor (VEGF) receptor (VEGFR) tyrosine kinase 1,2 and 3, is used in chemotherapy because it inhibits tumor angiogenesis by blocking the VEGF/VEGFR pathway. In veterinary medicine, attempts have been made to apply tyrosine kinase inhibitors with anti-angiogenic effects to tumor patients, but there are no studies on axitinib in canine mammary gland tumors (MGTs). Objectives: This study aimed to confirm the antitumor activity of axitinib in canine mammary gland cell lines. Methods: We treated canine MGT cell lines (CIPp and CIPm) with axitinib and conducted CCK, wound healing, apoptosis, and cell cycle assays. Additionally, we evaluated the expression levels of angiogenesis-associated factors, including VEGFs, PDGF-A, FGF-2, and TGF-β1, using quantitative real-time polymerase chain reaction. Furthermore, we collected canine peripheral blood mononuclear cells (PBMCs), activated them with concanavalin A (ConA) and lipopolysaccharide (LPS), and then treated them with axitinib to investigate changes in viability. Results: When axitinib was administered to CIPp and CIPm, cell viability significantly decreased at 24, 48, and 72 h (p < 0.001), and migration was markedly reduced (6 h, p < 0.05; 12 h, p < 0.005). The apoptosis rate significantly increased (p < 0.01), and the G2/M phase ratio showed a significant increase (p < 0.001). Additionally, there was no significant change in the viability of canine PBMCs treated with LPS and ConA. Conclusion: In this study, we confirmed the antitumor activity of axitinib against canine MGT cell lines. Accordingly, we suggest that axitinib can be applied as a new treatment for patients with canine MGTs.

Keywords

Acknowledgement

We thank the Seoul National University FACS Facility (NCIRF) for untiring efforts and perseverance.

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