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-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
张雪燕;艾子莺;苟泽鹏;陈静;易娟;赵怀顺;魏虎来
【期刊名称】《中国药理学通报》
【年(卷),期】2017(033)001
【摘要】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.%目的
研究2-脱氧葡萄糖（2-deoxy-D-glucose，2-DG）通过抑制糖代谢增强白血病
K562／ADM多药耐药细胞对阿霉素（adriamycin，ADM）敏感性的作用及机制。

方法以白血病K562／ADM及其亲本K562细胞为靶细胞模型，MTT法检测细胞增殖活性，葡萄糖、乳酸、己糖激酶测试盒分析葡萄糖消耗量、乳酸生成量和己糖激酶（hexokinase，HK）活性。

Western blot 法检测哺乳动物雷帕霉素靶蛋白（mammalian target of rapamycin，mTOR）表达和磷酸化（p-mTOR）以及
葡萄糖转运体-4（glucose transporter-4，GLUT-4）的表达。

结果与亲本K562细胞相比，白血病K562／ADM耐药细胞HK活性、GLUT-4表达水平和有氧糖
酵解能力增强。

2-DG能够明显抑制K562／ADM及K562细胞的HK活性、葡萄糖消耗量和乳酸生成量，呈时间－浓度依赖性地抑制白血病细胞的增殖活性。

低剂量2-DG和 ADM可诱导 K562／ADM细胞mTOR高表达及磷酸化水平增高，但2-DG与ADM联合则可有效对抗ADM诱导的K562／ADM细胞mTOR高表达
和磷酸化，并可降低GLUT-4的表达，提高K562／ADM细胞对阿霉素的敏感性。

结论2-DG通过竞争性抑制HK活性和抵抗ADM诱发的代偿性mTOR活化，降
低GLUT-4表达，有效阻断有氧糖酵解途径而降低K562／ADM耐药细胞的增殖活性、增强其对化疗药物的敏感性。

【总页数】7页(P126-132)
【作者】张雪燕;艾子莺;苟泽鹏;陈静;易娟;赵怀顺;魏虎来
【作者单位】兰州大学基础医学院，甘肃省新药临床前研究重点实验室;兰州大学基础医学院，甘肃省新药临床前研究重点实验室;兰州军区机关医院门诊部，甘肃兰州 730000;兰州大学基础医学院，甘肃省新药临床前研究重点实验室;兰州大学基础医学院，甘肃省新药临床前研究重点实验室;兰州大学基础医学院，甘肃省新药临床前研究重点实验室;兰州大学基础医学院，甘肃省新药临床前研究重点实验室
【正文语种】中文
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