细胞外 ATP 对顺铂诱导的人卵巢癌细胞毒性的影响。
Effect of extracellular ATP on cisplatin-induced cytotoxicity in human ovarian carcinoma cells.
机构信息
Department of Clinical Pharmacy, Institute of Pharmacy, University of Bonn, Bonn, Germany.
出版信息
Chemotherapy. 2010;56(1):1-8. doi: 10.1159/000287351. Epub 2010 Feb 24.
BACKGROUND
Cisplatin resistance has been mainly associated with decreased cellular accumulation and increased intracellular glutathione (GSH) levels. ATP is known to increase the membrane permeability of cells and to decrease intracellular GSH levels. Our study aimed at using extracellular ATP to sensitize ovarian carcinoma cells towards cisplatin.
METHODS
The MTT assay was used to determine the EC(50) of cisplatin in the human ovarian carcinoma cell line A2780 and its cisplatin-resistant variant A2780cis. Intracellular platinum concentrations were determined using flameless atomic absorption spectrometry.
RESULTS
Preincubation and concomitant incubation with ATP did not alter the EC(50) of cisplatin. The presence of 100 muM ATP along with cisplatin decreased cell survival in A2780 but not in A2780cis cells. Extracellular ATP did not increase the cellular accumulation of cisplatin in both A2780 and A2780cis cells.
CONCLUSION
The presence of extracellular ATP during treatment with cisplatin leads to additive cytotoxicity in the sensitive A2780 but not in cisplatin-resistant A2780cis cells.
背景
顺铂耐药性主要与细胞内蓄积减少和谷胱甘肽（GSH）水平升高有关。已知 ATP 可增加细胞的膜通透性并降低细胞内 GSH 水平。本研究旨在使用细胞外 ATP 使卵巢癌细胞对顺铂敏感。
方法
使用 MTT 法测定人卵巢癌细胞系 A2780 及其顺铂耐药变体 A2780cis 对顺铂的 EC50。使用无火焰原子吸收光谱法测定细胞内铂浓度。
结果
ATP 的预孵育和伴随孵育并未改变顺铂的 EC50。在存在 100 μM ATP 的情况下同时使用顺铂可降低 A2780 细胞的存活率，但对 A2780cis 细胞没有影响。细胞外 ATP 并未增加 A2780 和 A2780cis 细胞中顺铂的细胞内蓄积。
结论
在顺铂治疗期间存在细胞外 ATP 会导致敏感的 A2780 细胞产生附加的细胞毒性，但对顺铂耐药的 A2780cis 细胞没有影响。
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