title: Synergistic interaction between cisplatin and gemcitabine in neuroblastoma cell lines and multicellular tumor spheroids.
abstract: The efficacy and mechanism of action of cisplatin and gemcitabine were investigated in a panel of neuroblastoma cell lines and multicellular tumor spheroids. In neuroblastoma spheroids, the combination of cisplatin and gemcitabine induced a complete cytostasis at clinical relevant concentrations. A synergistic effect was observed when cells were coincubated with both drugs or preincubated with gemcitabine first. These administration sequences resulted in NASS cells in decreased ERCC1 and XPA expression, two key proteins of the NER DNA repair system, and increased platinum adduct formation in DNA. Most of these phenomena were not observed in SJNB8 cells which might explain the lack of synergy between cisplatin and gemcitabine in SJNB8 cells. Our results showed favorable interactions between cisplatin and gemcitabine in 4 out of 5 cell lines. Therefore, we feel that inclusion of gemcitabine into cisplatin-containing regiments might be a promising new strategy for the treatment of neuroblastoma.
authors.affiliation: Academic Medical Center, University of Amsterdam, Laboratory Genetic Metabolic Diseases, PO Box 22700, 1100 DE Amsterdam, The Netherlands.
authors.forename: Odette G
authors.initials: OG
authors.lastname: Besançon
authors.forename: Godelieve A M
authors.initials: GA
authors.lastname: Tytgat
authors.forename: Rutger
authors.initials: R
authors.lastname: Meinsma
authors.forename: René
authors.initials: R
authors.lastname: Leen
authors.forename: Jerry
authors.initials: J
authors.lastname: Hoebink
authors.forename: Ganna V
authors.initials: GV
authors.lastname: Kalayda
authors.forename: Ulrich
authors.initials: U
authors.lastname: Jaehde
authors.forename: Huib N
authors.initials: HN
authors.lastname: Caron
authors.forename: André B P
authors.initials: AB
authors.lastname: van Kuilenburg
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D004357:Drug Synergism; D006801:Humans; D009447:Neuroblastoma / Q000188:drug therapy*; D018874:Spheroids, Cellular / Q000187:drug effects*; D014407:Tumor Cells, Cultured; D000093542:Gemcitabine
chemical_list: D000970:Antineoplastic Agents; D003841:Deoxycytidine; D002945:Cisplatin; D000093542:Gemcitabine