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联合抑制mTORC2与热休克蛋白90对多发性骨髓瘤细胞增殖和凋亡的影响

Influence of Co-inhibiting mT0RC2 and HSP90 on Proliferation Apoptosis of Multiple Myeloma Cells

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【作者】 陈侃侃陈月何正梅周立涛张丽娟宋立孝丁邦和王春玲于亮周建伟

【Author】 CHEN Kan-Kan;CHEN Yue;HE Zheng-Mei;ZHOU Li-Tao;ZHANG Li-Juang;Song Li-Xiao;DING Bang-He;WANG Chun-Ling;YU Liang;ZHOU Jian-Wei;School of Public Health,Nanjing Medical University;Department of Hematology,Huaian First Affiliated Hospital of Nanjing Medical University;

【机构】 南京医科大学公共卫生学院南京医科大学附属淮安第一医院血液科

【摘要】 目的:探讨m TORC2与HSP90共同受抑对多发性骨髓瘤细胞增殖和凋亡的影响。方法:人多发性骨髓瘤细胞株U266细胞在培养过程中分别加入雷帕霉素20 nmol/L、17-AAG 600 nmol/L、雷帕霉素20 nmol/L+17-AAG600 nmol/L、PBS溶液进行干预,比较各组的细胞抑制率、形态变化、凋亡率以及caspase-3和AKT蛋白的表达。结果:联合使用雷帕霉素和17-AAG对多发性骨髓瘤细胞生长抑制作用明显的大于单一使用相同浓度相应药物;雷帕霉素、17-AAG及两药联合干预组细胞的凋亡率明显的大于PBS对照组,并且联合用药干预细胞的凋亡率明显大于单一使用相同浓度相应药物的干预细胞的凋亡率;雷帕霉素、17-AAG及两药联合干预组U266细胞的caspase-3蛋白表达明显的大于PBS对照组,并且联合用药干预细胞中caspase-3蛋白表达明显大于单一使用相同浓度相应药物;雷帕霉素、17-AAG及两药联合干预组U266细胞AKT蛋白表达明显小于对照组,联合用药干预组细胞AKT蛋白表达明显小于单一使用相同浓度相应药物,其差异均具有显著性(P<0.05)。结论:联合抑制m TORC2与HSP90能抑制多发性骨髓瘤细胞的增殖并且诱导细胞的凋亡。

【Abstract】 Objective:To explore the influence of co-inhibiting mT0RC2 and HSP90 on the proliferation and apoptosis of multiple myeloma(MM) cell line U266.Methods:During culture,the human MM cell line U266 were treated with 20 nmol/L of rapamycin,600 nmol/L 17-AAG,20 nmol/L of rapamycin + 600 nmol/L 17-AGG and phosphate-buffered saline(PBS),then the growth inhibition rate,morphologic changes,apoptosis rate and the expression of caspase 3 and ATK protein in U266 cells were compared and analyzed.Results:The rapamycin and 17-AAG both could inhibit the growth of U266 cells,while the inhibitory effect of rapamycin in combination with 17-AAG on growth of U266 cells was significantly higher them that of rapamycin and 17-AAG alone and control(PBS);the apoptosis rate of U266 cells treated with rapamycin,17-AAG and their combination was higher than that of control PBS groups,and the efficacy of 2 drug conbination was higher than that of control PBS group,and the efficacy of 2 drug combination was superior to single drug.The expression levels of caspase 3 and ATK in U266 cells treated with rapamycin,17-AAG and their combination were higher and lower than those in control group respectively,and the efficacy of 2 drug combination was superior to signle drug.There were significant difference between them(P <0.05).Conclusion:The co-inhibition of mT0RC2 and HSP90 can suppress the proliferation and induce the apoptosis of MM cells.

【关键词】 mTORC2HSP90多发性骨髓瘤凋亡
【Key words】 apoptosismTORC2HSP90multiple myeloma
【基金】 基金项目:BK20141254
  • 【文献出处】 中国实验血液学杂志 ,Journal of Experimental Hematology , 编辑部邮箱 ,2016年04期
  • 【分类号】R733.3
  • 【被引频次】2
  • 【下载频次】137
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