Synergistic interaction between cisplatin and gemcitabine in neuroblastoma cell lines and multicellular tumor spheroids

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...

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Bibliographic Details
Published in:Cancer letters 2012-06, Vol.319 (1), p.23-30
Main Authors: Besançon, Odette G, Tytgat, Godelieve A.M, Meinsma, Rutger, Leen, René, Hoebink, Jerry, Kalayda, Ganna V, Jaehde, Ulrich, Caron, Huib N, van Kuilenburg, André B.P
Format: Article
Language:English
Subjects:
Antineoplastic Agents - pharmacology
Cancer
Cancer therapies
Cell Line, Tumor
Cisplatin
Cisplatin - pharmacology
Deoxycytidine - analogs & derivatives
Deoxycytidine - pharmacology
Deoxyribonucleic acid
DNA
DNA repair
Drug interactions
Drug Screening Assays, Antitumor
Drug Synergism
Gemcitabine
Hematology, Oncology and Palliative Medicine
Humans
mechanism of action
Neuroblastoma
Neuroblastoma - drug therapy
platinum
proteins
Ribonucleotide reductase
Spheroids
Spheroids, Cellular - drug effects
synergism
Tumor Cells, Cultured
Tumors
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Summary: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.
ISSN:0304-3835
1872-7980
DOI:10.1016/j.canlet.2011.12.016