Intracellular free calcium concentration and cisplatin resistance in human lung adenocarcinoma A549 cells.

Human lung adenocarcinoma A549 cells sensitive and A549/DDP cells resistant to Cis-dichlorodiammine platinum[II] (cisplatin) exhibit different intracellular free calcium and calcium fluorescence images labeled with Fura-2/AM and Fluo-3/AM as judged by dual-excitation fluorescence assay, Miracal Imaging and Laser Scanning Confocal Microscopy (LSCM) of single cells. The concentration of intracellular free calcium of the resistant A549/ DDP cells is one third that of the sensitive A549 cells. The efflux of Rhodamine 123 in resistant A549/DDP cells is faster than that in sensitive A549 cells. In addition, A549/DDP cells have an increase of Phosphatidylinositol 4-kinase (PtdIns 4-kinase) activity in the plasma membrane. So it is tentatively suggested that the increase in PtIns 4-kinase activity resulting from lower intracellular Ca2+ concentration leads to an increase of its enzymatic products--PIP and PIP2, which may stimulate the activity of P-glycoprotein.