title: Enrofloxacin enhances the effects of chemotherapy in canine osteosarcoma cells with mutant and wild-type p53.
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.
authors.affiliation: The Comparative Oncology Laboratory and Center for Companion Animal Health, Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California-Davis, Davis, CA, USA.
authors.forename: D
authors.initials: D
authors.lastname: York
authors.affiliation: The Comparative Oncology Laboratory and Center for Companion Animal Health, Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California-Davis, Davis, CA, USA.
authors.forename: S S
authors.initials: SS
authors.lastname: Withers
authors.affiliation: UC Davis School of Veterinary Medicine, William R. Pritchard Veterinary Medical Teaching Hospital, University of California-Davis, Davis, CA, USA.
authors.forename: K D
authors.initials: KD
authors.lastname: Watson
authors.affiliation: Department of Veterinary Internal Medicine, College of Veterinary Medicine, Chungnam National University, Daejon, Korea.
authors.forename: K W
authors.initials: KW
authors.lastname: Seo
authors.affiliation: The Comparative Oncology Laboratory and Center for Companion Animal Health, Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California-Davis, Davis, CA, USA.
authors.forename: R B
authors.initials: RB
authors.lastname: Rebhun
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000662:veterinary*; D016190:Carboplatin / Q000008:administration & dosage / Q000627:therapeutic use; D045744:Cell Line, Tumor; D017024:Chemotherapy, Adjuvant / Q000662:veterinary; D004283:Dog Diseases / Q000188:drug therapy* / Q000235:genetics; D004285:Dogs; D004317:Doxorubicin / Q000008:administration & dosage / Q000627:therapeutic use; D000077422:Enrofloxacin; D024841:Fluoroquinolones / Q000008:administration & dosage / Q000627:therapeutic use*; D012516:Osteosarcoma / Q000188:drug therapy / Q000235:genetics / Q000662:veterinary*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: D000970:Antineoplastic Agents; D024841:Fluoroquinolones; D016159:Tumor Suppressor Protein p53; D000077422:Enrofloxacin; D004317:Doxorubicin; D016190:Carboplatin
keywords: chemotherapy; comparative oncology; oncology; small animal; tumour biology