title: Meglumine Eicosapentaenoic acid (MeEPA) a new soluble omega-3 fatty acid formulation: in vitro bladder cancer cytotoxicity tests in combination with epirubicin and mitomycin.
abstract: OBJECTIVE
  To determine if Meglumine-Eicosapentaenoic Acid (MeEPA) acts synergistically with epirubicin and mitomycin to enhance cytotoxicity towards bladder cancer cell lines in vitro.
  
  
  METHODS
  Bladder cancer cells were exposed to MeEPA in combination with epirubicin or mitomycin. Residual viable cell biomass was estimated with the methyl-thiazoldiphenyl tetrazolium (MTT) assay following drug exposure. Drug interaction was analysed using median effect analysis to determine levels of synergism.
  
  
  RESULTS
  Most combinations of MeEPA with both epirubicin and mitomycin showed a high-level of synergism. At high doses, drug precipitation adversely affected MTT assay analysis suggesting antagonism of action. However, the predominant pattern was of synergism for most dose combinations tested.
  
  
  CONCLUSIONS
  Bladder cancer treated by endoscopic resection alone is subject to high recurrence rates. Post-operative intravesical instillation of epirubicin and mitomycin can halve recurrence rates, but there is no evidence that disease progression to invasive bladder cancer is altered. Thus, optimisation of current treatment strategies is required. The anti-tumour activity of fatty acids is well established and MeEPA is a new, soluble formulation with the potential to enhance intravesical drug efficacy.
authors.affiliation: Portsmouth University and The Solent Department of Urology, Portsmouth NHS Trust, Hampshire, UK. mackie@doctors.org.uk
authors.forename: S J
authors.initials: SJ
authors.lastname: Mackie
authors.forename: D M
authors.initials: DM
authors.lastname: Sharma
authors.forename: A J
authors.initials: AJ
authors.lastname: Cooper
authors.forename: N M
authors.initials: NM
authors.lastname: Harris
authors.forename: B A
authors.initials: BA
authors.lastname: Lwaleed
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols; D045744:Cell Line, Tumor; D004338:Drug Combinations; D004354:Drug Screening Assays, Antitumor; D004357:Drug Synergism; D015118:Eicosapentaenoic Acid / Q000627:therapeutic use*; D015251:Epirubicin / Q000627:therapeutic use*; D015525:Fatty Acids, Omega-3 / Q000627:therapeutic use; D006801:Humans; D008536:Meglumine / Q000627:therapeutic use*; D016685:Mitomycin / Q000627:therapeutic use*; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy*
chemical_list: D000903:Antibiotics, Antineoplastic; D004338:Drug Combinations; D015525:Fatty Acids, Omega-3; C517011:meglumine-eicosapentaenoic acid formulation; D015251:Epirubicin; D016685:Mitomycin; D008536:Meglumine; D015118:Eicosapentaenoic Acid