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.
Liang
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X
National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing.
Huang
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Y
D019870:1-Phosphatidylinositol 4-Kinase / Q000378:metabolism; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000230:Adenocarcinoma / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D002118:Calcium / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D002945:Cisplatin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D016257:Fura-2 / Q000378:metabolism; D006801:Humans; D007424:Intracellular Fluid / Q000378:metabolism*; D007700:Kinetics; D008175:Lung Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D018613:Microscopy, Confocal; D010716:Phosphatidylinositols / Q000378:metabolism; D020112:Rhodamine 123 / Q000378:metabolism; D014407:Tumor Cells, Cultured
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D010716:Phosphatidylinositols; D020112:Rhodamine 123; D019870:1-Phosphatidylinositol 4-Kinase; D002945:Cisplatin; D002118:Calcium; D016257:Fura-2