中国药理学通报2017，Vol.33Issue(1)：126-132,7.DOI:10.3969/j.issn.1001-1978.2017.01.022
2-脱氧葡萄糖通过降低有氧糖酵解增强白血病K562／ADM耐药细胞对阿霉素的敏感性
2-Deoxyglucose improves sensitivity of leukemia drug-resistant K562/ADM cells to adriamycin by blocking aerobic glycolysis
摘要
Abstract
Aim To investigate the effect of 2-deoxy-D-glucose(2-DG)on the sensitivity of leukemia multi-drug resistant K562/ADMcells to adriamycin by inhib-iting glycolytic pathway as well as its molecular mecha-nisms.Methods The leukemia drug-resistant K562/ADM cells and parental K562 cells were used as the target cell models.The cell proliferating activity was assessed with an MTT colorimetric assay,and the gly-colysis including glucose consumption,lactate export, and hexokinase activity was determined by glucose, lactic acid and hexokinase (HK)testing kits.The ex-pression and phosphorylation of mammalian target of rapamycin(mTOR)and glucose transporter-4 (GLUT-4)expression were analyzed by western blot.Results K562/ADM drug-resistant cells possessed higher HK activity,GLUT-4 expression level and aerobic glycolic ability than K562 sensitive cells. 2-DG treatment markedly inhibited HK activity,glucose consumption, and lactate export both in K562 cells and K562/ADM cells,and suppressed the proliferation of the two cells in a time-and concentration-dependent manner.Low concentration of 2-DG or adriamycin could increase the expression and phosphorylation of mTOR.However, the co-administration of 2-DG and adriamycin markedly counteracted adriamycin-mediated enhancement of mTOR expression and phosphorylation and down-regu-lated GLUT-4 expression in K562/ADM cells,and 2-DG dramatically improved the sensitivity of K562/ADM cells to cytotoxicity.Conclusion 2-DG inhibits the proliferation of drug-resistant K562/ADM cells and en-hances the sensitivity to adriamycin by blocking aerobic glycolysis pathway through inhibiting hexokinase activi-ty,counteracting adriamycin-stimulated increased ex-pression and phosphorylation of mTOR and downregu-lating GLUT-4 expression.关键词
2-脱氧葡萄糖/阿霉素/多药耐药性/有氧糖酵解/mTOR/GLUT-4/白血病Key words
2-deoxy-D-glucose/adriamycin/multidrug resistance/aerobic glycolysis/mTOR/GLUT-4/leuke-mia引用本文复制引用
张雪燕,艾子莺,苟泽鹏,陈静,易娟,赵怀顺,魏虎来..2-脱氧葡萄糖通过降低有氧糖酵解增强白血病K562／ADM耐药细胞对阿霉素的敏感性[J].中国药理学通报,2017,33(1):126-132,7.基金项目
国家自然科学基金资助项目（No 81541025，81141053）；兰州大学中央高校基本科研业务费专项资金资助项目 （）
