Intracellular Free Calcium Concentration and Cisplatin Resistance in Human Lung Adenocarcinoma A549 Cells

Abstract

Human lung adenocarcinoma A549 cells sensitive and A549/DDP cells resistantto Cis-dichlorodiammine platinum[II] (cisplatin) exhibit differentintracellular free calcium and calcium fluorescence images labeled withFura-2/AM and Fluo-3/AM as judged by dual-excitation fluorescence assay,Miracal Imaging and Laser Scanning Confocal Microscopy (LSCM) of singlecells. The concentration of intracellular free calcium of the resistantA549/DDP cells is one third that of the sensitive A549 cells. The effluxof Rhodamine 123 in resistant A549/DDP cells is faster than that insensitive A549 cells. In addition, A549/DDP cells have an increase ofPhosphatidylinositol 4-kinase (PtdIns 4-kinase) activity in the plasmamembrane. So it is tentatively suggested that the increase in PtIns4-kinase activity resulting from lower intracellular Ca2+concentration leads to an increase of its enzymaticproducts”�”�PIP and PIP2, which may stimulate the activity ofP-glycoprotein.