Properties of amino acid transport systems in K562 cells sensitive and resistant to cis-diamminedichloroplatinum(II).-猫眼课题宝

K562 细胞中氨基酸转运系统对顺式二氯铂 (II) 敏感和耐药的特性。

DOI：

发表时间：

1986

期刊：

Cancer Research

影响因子：

11.2

通讯作者：

中科院分区：

医学1区

文献类型：

作者：

S. Shionoya;Y. Lu;K. Scanlon

当K562细胞对顺铂耐药时，其中性氨基酸转运系统发生变化。在顺铂中克隆的K562细胞对该药物产生了6.7倍的耐药性。K562细胞对顺铂敏感（S）和耐药（DDP）的传代时间相似。顺铂的初始摄取和快速外排在两种细胞系中是相似的。然而，它们的钠依赖性中性氨基酸转运特性不同。在K562 S细胞中，钠依赖性摄取甲基氨基异丁酸被苏氨酸显著抑制（Ki = 10.3 mM），但在K562 DDP中，中性氨基酸的摄取显著降低，甲基氨基异丁酸的摄取被苏氨酸抑制最小。当K562 DDP细胞在顺铂的情况下生长8周，其氨基酸转运特性恢复到K562 S细胞。在K562细胞中，质膜必需氨基酸转运系统的变化是伴随着对顺铂的耐药性和敏感性的发展。因此，人恶性肿瘤细胞对顺铂的敏感性和耐药性可能与细胞膜营养转运系统有关。

When K562 cells were made resistant to cisplatin their neutral amino acid transport systems changed. K562 cells cloned in cisplatin developed a 6.7-fold resistance to the drug. The generation times for K562 cells sensitive (S) and resistant (DDP) to cisplatin were similar. The initial uptake and rapid efflux of cisplatin were similar in both cell lines. However, they differed in their sodium dependent neutral amino acid transport properties. In K562S cells the sodium-dependent uptake for methylaminoisobutyric acid was significantly inhibited by threonine (Ki = 10.3 mM), but in K562DDP the uptake of neutral amino acids was significantly lower, and methylaminoisobutyric acid uptake was minimally inhibited by threonine. When K562DDP cells were grown in the absence of cisplatin for 8 weeks, their amino acid transport properties reverted to those of K562S cells. In K562 cells, changes in plasma membrane essential amino acid transport systems were concomitant to both the development of resistance and the redevelopment of sensitivity to cisplatin. Therefore, human malignant cell sensitivity and resistance to cisplatin may be related to membrane nutrient transport systems.

Antibodies elicited against cis-diamminedichloroplatinum(II)-modified DNA are specific for cis-diamminedichloroplatinum(II)-DNA adducts formed in vivo and in vitro.