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

Abstract

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.