Biological activity of gemcitabine against canine osteosarcoma cell lines in vitro.
OBJECTIVE
To evaluate in vitro biological activity of gemcitabine, alone and in combination with Pamidronate or carboplatin, against canine osteosarcoma (OSA) cell lines.


METHODS
In vitro cultures of OSA cell lines OSA8, OSA16, OSA32, and OSA36.


METHODS
Cell lines were treated with gemcitabine alone or in combination with pamidronate or carboplatin. Cell viability was assessed with the water soluble tetrazolium-1 (WST-1) assay, cell cycle distribution was evaluated by means of propidium iodide staining, and apoptosis was assessed by measuring caspase-3/7 activity. Synergy was quantified by use of combination index (CI) analysis.


RESULTS
For all of the cell lines, treatment with gemcitabine induced growth inhibition, cell cycle arrest, and apoptosis. No synergistic or additive activity was identified when OSA cell lines were treated with gemcitabine in combination with pamidronate. However, when OSA cell lines were treated with gemcitabine in combination with carboplatin, a significant decrease in cell viability was observed, compared with treatment with carboplatin alone, and the drug combination was determined to be synergistic on the basis of results of CI analysis. For 3 of the 4 cell lines, this activity was greater when cells were treated with carboplatin prior to gemcitabine rather than with gemcitabine prior to carboplatin.


CONCLUSIONS
Gemcitabine exhibited biological activity against canine OSA cell lines in vitro, and a combination of gemcitabine and carboplatin exhibited synergistic activity at biologically relevant concentrations. Findings support future clinical trials of gemcitabine alone or in combination with carboplatin for the treatment of dogs with OSA.
McMahon
Melanie B
MB
Department of Veterinary Clinical Sciences, The Ohio State University, Columbus, OH 43210, USA.
Bear
Misty D
MD
Kulp
Samuel K
SK
Pennell
Michael L
ML
London
Cheryl A
CA
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D001859:Bone Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000662:veterinary*; D016190:Carboplatin / Q000627:therapeutic use; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004164:Diphosphonates / Q000627:therapeutic use; D004283:Dog Diseases / Q000188:drug therapy*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D012516:Osteosarcoma / Q000188:drug therapy / Q000473:pathology / Q000662:veterinary*; D000077268:Pamidronate; D000093542:Gemcitabine
D000893:Anti-Inflammatory Agents; D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D004164:Diphosphonates; D003841:Deoxycytidine; D016190:Carboplatin; D000077268:Pamidronate; D000093542:Gemcitabine