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Canine osteosarcoma cells exhibit resistance to aurora kinase inhibitors

C M Cannon1, J Pozniak, M C Scott

  • 1Department of Veterinary Clinical Sciences, College of Veterinary Medicine, University of Minnesota, St Paul, MN, USA.

Veterinary and Comparative Oncology
|February 16, 2013
PubMed

Insights

Canine osteosarcoma cells show resistance to Aurora kinase inhibitors AZD1152 and VX680. These drugs are unlikely effective as single agents for canine osteosarcoma, warranting further research into resistance mechanisms.

Area of Science:

  • Oncology
  • Pharmacology
  • Cell Biology

Background:

  • Aurora kinase inhibitors are investigated for cancer therapy.
  • Canine osteosarcoma is an aggressive bone cancer.
  • Understanding drug resistance is crucial for effective treatment.

Purpose of the Study:

  • To evaluate the efficacy of Aurora kinase inhibitors AZD1152 and VX680 against canine osteosarcoma cells.
  • To investigate potential mechanisms of resistance in these cells.

Main Methods:

  • Cytotoxicity assays were performed on four canine osteosarcoma cell lines.
  • Aurora kinase B phosphorylation was assessed.
  • The role of ABCB1 and ABCG2 transporters in resistance was evaluated using verapamil.

Main Results:

  • Canine osteosarcoma cells exhibited resistance to AZD1152 and VX680, with higher half-maximal inhibitory concentrations compared to human leukaemia and canine lymphoma cells.
  • AZD1152 effectively reduced Aurora kinase B phosphorylation, ruling out target recognition failure as the primary resistance mechanism.
  • While ABCB1 and ABCG2 transporter activity was observed, its contribution to resistance was modest, suggesting other mechanisms are involved.

Conclusions:

  • Canine osteosarcoma cells display significant resistance to Aurora kinase inhibitors.
  • These inhibitors are unlikely to be effective as monotherapy for canine osteosarcoma.
  • Further research into resistance mechanisms and combination therapies is recommended.
Keywords:
chemotherapycomparative oncologyin vitro modelsoncologyosteosarcoma

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