Modulation of cisplatin resistance by 2'-deoxy-5-azacytidine in human ovarian tumor cell lines.
Modulation of cisplatin resistance by 2'-deoxy-5-azacytidine in human ovarian tumor cell lines.
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发表时间：
1994
影响因子：
2
通讯作者：
R. Lenzi;P. Frost;J. Abbruzzese
中科院分区：
文献类型：
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作者：
R. Lenzi;P. Frost;J. Abbruzzese
2 ′-脱氧-5-氮杂胞苷（DAC）和顺铂的顺序给药经常导致对人癌细胞系（包括顺铂抗性HEY卵巢癌细胞系）的协同细胞毒性（Frost P，et al Cancer Res 50：4572-4577，1990）。在这一系列体外实验中，在两种顺铂抗性卵巢细胞系C13* 和A2780/DDP中，并通过改变DAC与顺铂对HEY细胞系的浓度比，评价DAC对顺铂抗性的影响。对于C13* 和A2780/DDP，连续暴露于DAC和顺铂导致协同作用，并使达到规定细胞毒性水平所需的顺铂浓度降低1 - 3倍。在HEY系中也观察到协同相互作用的增强，这表明相对于顺铂增加DAC的浓度可以导致一些高度顺铂抗性系的顺铂抗性的调节改善。由于在体外观察这些相互作用所需的DAC和顺铂浓度通常在人血浆中可达到，因此可以在适当设计的临床试验中检测DAC调节顺铂耐药性的临床价值。
The sequential administration of 2'-deoxy-5-azacytidine (DAC) and cisplatin frequently results in synergistic cytotoxicity against human cancer cell lines (Frost P, et al Cancer Res 50:4572-4577, 1990) including the cisplatin resistant HEY ovarian cancer cell line. In this series of in vitro experiments the effect of DAC on cisplatin resistance was evaluated in two cisplatin resistant ovarian cell lines, C13* and A2780/DDP, and by varying the concentration ratio of DAC to cisplatin against the HEY cell line. For C13* and A2780/DDP sequential exposure to DAC and cisplatin resulted in synergy and a one to three-fold decrease in the concentration of cisplatin required to achieve defined levels of cytotoxicity. Augmentation of the synergistic interaction was also observed with the HEY line suggesting that increasing the concentration of DAC relative to cisplatin could result in improved modulation of cisplatin resistance for some highly cisplatin resistant lines. Since the concentrations of DAC and cisplatin required in vitro to observe these interactions are frequently achievable in human plasma, the clinical value of DAC modulation of cisplatin resistance could be tested in appropriately designed clinical trials.