Synergistic interaction between cisplatin and gemcitabine in neuroblastoma cell lines and multicellular tumor spheroids
Synergistic interaction between cisplatin and gemcitabine in neuroblastoma cell lines and multicellular tumor spheroids
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DOI：
10.1016/j.canlet.2011.12.016
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发表时间：
2012-06-01
期刊：
影响因子：
9.7
通讯作者：
van Kuilenburg, Andre B. P.
中科院分区：
文献类型：
--
作者：
Besancon, Odette G.;Tytgat, Godelieve A. M.;van Kuilenburg, Andre B. P.
在一组神经母细胞瘤细胞系和多细胞肿瘤球体中研究了顺铂和吉西他滨的疗效和作用机制。在神经母细胞瘤球状体中，顺铂和吉西他滨的组合在临床相关浓度下诱导完全细胞抑制。当细胞与两种药物共孵育或先与吉西他滨预孵育时，观察到协同效应。这些给药序列导致NASS细胞ERCC1和XPA表达降低，这两种蛋白质是NER DNA修复系统的关键蛋白质，并增加了DNA中铂加合物的形成。在SJNB8细胞中没有观察到这些现象中的大多数，这可能解释了顺铂和吉西他滨在SJNB8细胞中缺乏协同作用。我们的研究结果表明，顺铂和吉西他滨之间的有利相互作用，在4个5细胞系。因此，我们认为将吉西他滨纳入含顺铂的方案可能是治疗神经母细胞瘤的一个有前途的新策略。(c)2011爱思唯尔爱尔兰有限公司保留所有权利。
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. (c) 2011 Elsevier Ireland Ltd. All rights reserved.