Antitumor Activity of Rivoceranib Against Canine Mammary Gland Tumor Cell Lines

Anticancer Res. 2019 Oct;39(10):5483-5494. doi: 10.21873/anticanres.13741.

Abstract

Background/aim: Canine mammary gland tumors (CMGTs) are the most common tumors in female dogs. Rivoceranib (also known as apatinib) is a novel anti-angiogenic tyrosine kinase inhibitor that selectively binds to vascular endothelial growth factor receptor-2 (VEGFR2). The aim of this study was to disclose the antitumor effects of rivoceranib on CMGT cell lines.

Materials and methods: The direct effects of rivoceranib on CMGT cells in vitro were analyzed by cell proliferation and migration assays. Cell-cycle distribution and apoptotic ratio were analyzed by flow cytometry. Expression levels of phosphorylated VEGFR2 were evaluated by western blot analysis.

Results: Rivoceranib treatment significantly reduced the proliferation and migration of CMGT cells in a dose-dependent manner. Flow cytometry results revealed significant increases in G0/G1 phase arrest and apoptosis proportional to the drug concentration used. Rivoceranib reduced the level of phosphorylated VEGFR2.

Conclusion: We confirm that rivoceranib exerts antitumor effects on CMGT cells by inhibiting biological functions.

Keywords: Apatinib; VEGF; antitumor; canine mammary gland tumor cell; migration; pVEGFR2; rivoceranib.

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Cell Cycle Checkpoints / drug effects
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Dogs
  • Female
  • G1 Phase / drug effects
  • Mammary Neoplasms, Animal / drug therapy*
  • Mammary Neoplasms, Animal / metabolism
  • Phosphorylation / drug effects
  • Protein Kinase Inhibitors / pharmacology*
  • Pyridines / pharmacology*
  • Resting Phase, Cell Cycle / drug effects
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Antineoplastic Agents
  • Protein Kinase Inhibitors
  • Pyridines
  • Vascular Endothelial Growth Factor A
  • apatinib