Enrofloxacin enhances the effects of chemotherapy in canine osteosarcoma cells with mutant and wild-type p53

Vet Comp Oncol. 2017 Sep;15(3):1087-1100. doi: 10.1111/vco.12250. Epub 2016 Jun 23.

Abstract

Adjuvant chemotherapy improves survival time in dogs receiving adequate local control for appendicular osteosarcoma, but most dogs ultimately succumb to metastatic disease. The fluoroquinolone antibiotic enrofloxacin has been shown to inhibit survival and proliferation of canine osteosarcoma cells in vitro. Others have reported that fluoroquinolones may modulate cellular responses to DNA damaging agents and that these effects may be differentially mediated by p53 activity. We therefore determined p53 status and activity in three canine osteosarcoma cell lines and examined the effects of enrofloxacin when used alone or in combination with doxorubicin or carboplatin chemotherapy. Moresco and Abrams canine osteosarcoma cell lines contained mutations in p53, while no mutations were identified in the D17 cells or in a normal canine osteoblast cell line. The addition of enrofloxacin to either doxorubicin or carboplatin resulted in further reductions in osteosarcoma cell viability; this effect was apparent regardless of p53 mutational status or downstream activity.

Keywords: chemotherapy; comparative oncology; oncology; small animal; tumour biology.

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / therapeutic use*
  • Bone Neoplasms / drug therapy
  • Bone Neoplasms / genetics
  • Bone Neoplasms / veterinary*
  • Carboplatin / administration & dosage
  • Carboplatin / therapeutic use
  • Cell Line, Tumor
  • Chemotherapy, Adjuvant / veterinary
  • Dog Diseases / drug therapy*
  • Dog Diseases / genetics
  • Dogs
  • Doxorubicin / administration & dosage
  • Doxorubicin / therapeutic use
  • Enrofloxacin
  • Fluoroquinolones / administration & dosage
  • Fluoroquinolones / therapeutic use*
  • Osteosarcoma / drug therapy
  • Osteosarcoma / genetics
  • Osteosarcoma / veterinary*
  • Tumor Suppressor Protein p53 / genetics*

Substances

  • Antineoplastic Agents
  • Fluoroquinolones
  • Tumor Suppressor Protein p53
  • Enrofloxacin
  • Doxorubicin
  • Carboplatin