title: Effects of gemcitabine and gemcitabine in combination with carboplatin on five canine transitional cell carcinoma cell lines.
abstract: OBJECTIVE
  To evaluate in vitro effects of gemcitabine alone and in combination with carboplatin on canine transitional cell carcinoma (TCC) cell lines.
  
  
  METHODS
  In vitro cultures of 5 canine TCC cell lines.
  
  
  METHODS
  Cells were treated with gemcitabine, carboplatin, or a combination of both at various concentrations. Cell proliferation was assessed via a fluorescence-based microplate cell proliferation assay. Cell cycle was evaluated via propidium iodide staining, and apoptosis was assessed by measurement of caspase 3 and 7 enzymatic activity. Synergy between gemcitabine and carboplatin was quantified via combination index analyses.
  
  
  RESULTS
  Treatment of 5 canine TCC cell lines with gemcitabine or carboplatin decreased cell proliferation, increased apoptosis, and induced cell cycle arrest. Cell cycle arrest and apoptosis were markedly increased when cell lines were treated with both gemcitabine and carboplatin simultaneously or sequentially. Order of administration during sequential treatment did not consistently affect cell proliferation results in TCC cell lines. When TCC cell lines were treated with gemcitabine and carboplatin in combination at therapeutically relevant concentrations (gemcitabine concentration, < 10μM; carboplatin concentration, < 250μM), a significant decrease in cell proliferation was observed, compared with cell proliferation following treatment with gemcitabine or carboplatin alone. In combination, the effects of gemcitabine and carboplatin were synergistic in 3 of 5 cell lines and additive in the other 2.
  
  
  CONCLUSIONS
  Gemcitabine had antitumor effects on canine TCC cells in vitro, and the combination of gemcitabine and carboplatin had synergistic activity at biologically achievable concentrations.
authors: Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210, USA.
authors: Joao Felipe
authors: JF
authors: de Brito Galvao
authors: William C
authors: WC
authors: Kisseberth
authors: Sridhar
authors: S
authors: Murahari
authors: Saikaew
authors: S
authors: Sutayatram
authors: Dennis J
authors: DJ
authors: Chew
authors: Nongnuch
authors: N
authors: Inpanbutr
mesh_terms: D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis; D016190:Carboplatin / Q000627:therapeutic use; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy*; D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004283:Dog Diseases / Q000188:drug therapy*; D004285:Dogs; D004357:Drug Synergism; D004359:Drug Therapy, Combination / Q000662:veterinary; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D003841:Deoxycytidine; D016190:Carboplatin; D000093542:Gemcitabine