cis-Diamminedichloroplatinum(II) accumulation in sensitive and resistant human ovarian carcinoma cells.
cis-Diamminedichloroplatinum(II) accumulation in sensitive and resistant human ovarian carcinoma cells.
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发表时间：
1988
期刊：
影响因子：
11.2
通讯作者：
P. Andrews;S. Velury;S. Mann;S. Howell
中科院分区：
文献类型：
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作者：
P. Andrews;S. Velury;S. Mann;S. Howell
我们描述了顺铂（DDP）在亲本和顺铂耐药2008人卵巢癌细胞中的积累。在两种细胞类型中，DDP在1 h内的积累量与浓度为0.25 ~ 100微米的DDP呈线性关系。耐ddp的细胞在所有检测浓度下的铂累积量都减少了约50%。在两种细胞类型中，1.0微米DDP的积累在大约3小时内呈线性增长，然后缓慢增长，但在24小时内没有达到平衡。耐药细胞中DDP积累的减少似乎不是由于外排增加；在亲本细胞和抗性细胞中，可获得相似百分比的铂。耐药细胞内的DDP代谢物似乎减少了相似的量。原生DDP不受浓度梯度驱使上坡进入细胞，这表明DDP摄取不涉及主要的主动运输。代谢抑制剂二硝基酚和NaF对DDP积累没有抑制作用；碘乙酸酯有刺激作用。然而，二硝基苯酚与NaF或碘乙酸酯联合使用可减少DDP的积累。暴露于0.2 mM瓦巴因30分钟也减少了亲本和抗性细胞中DDP的积累。因此，国内生产总值积累的一个组成部分似乎依赖于能源。这些研究已经确定DDP积累减少是一个重要的耐药机制，在人卵巢癌细胞获得DDP耐药的早期表达。
We have characterized the accumulation of cisplatin (DDP) into parent and cisplatin-resistant 2008 human ovarian carcinoma cells. Accumulation of DDP at 1 h was a linear function of concentration from 0.25 to 100 microM DDP in both cell types. DDP-resistant cells that were only 3.3-fold resistant had approximately 50% less accumulated platinum at all concentrations examined. Accumulation of 1.0 microM DDP was linear for approximately 3 h and then slowed but did not reach equilibrium at up to 24 h in either cell type. The decreased DDP accumulation in resistant cells did not appear to be due to increased efflux; similar percentages of platinum were available for exodus in parent and resistant cells. Intracellular metabolites of DDP appeared to be decreased by similar amounts in the resistant cells. Native DDP was not driven uphill into cells against a concentration gradient, suggesting that DDP uptake does not involve primary active transport. The metabolic inhibitors, dinitrophenol and NaF, did not decrease DDP accumulation; iodoacetate had a stimulatory effect. Dinitrophenol, however, in combination with NaF or iodoacetate decreased DDP accumulation. A 30-min exposure to 0.2 mM ouabain also decreased DDP accumulation in both parent and resistant cells. A component of DDP accumulation thus appears to be energy dependent. These studies have identified decreased DDP accumulation as an important mechanism of resistance that is expressed early in the acquisition of DDP resistance in human ovarian carcinoma cells.