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.
journal_name
Cancer Lettjournal_title
Cancer lettersauthors
Besançon OG,Tytgat GA,Meinsma R,Leen R,Hoebink J,Kalayda GV,Jaehde U,Caron HN,van Kuilenburg ABdoi
10.1016/j.canlet.2011.12.016subject
Has Abstractpub_date
2012-06-01 00:00:00pages
23-30issue
1eissn
0304-3835issn
1872-7980pii
S0304-3835(11)00763-4journal_volume
319pub_type
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