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CD44单克隆抗体A3D8通过抑制ERK1/2上调Bim诱导HL-60细胞早期凋亡 被引量：1

Early Apoptosis of HL-60 Cells Induced by Anti-CD44 McAb A3D8 Inhibiting ERK1/2-Upregulated Bim Expression
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摘要 CD44单克隆抗体A3D8可抑制急性髓系白血病(acute myeloid leukemia,AML)细胞的增殖抑制,并诱导其早期凋亡。本研究探讨在此过程中ERK以及BCL-2家族成员的作用机制,为治疗白血病提供新方法和新的药物靶点。用MTT法检测A3D8对HL-60细胞的增殖抑制效应,用流式细胞术检测A3D8对HL-60细胞线粒体膜电位的变化,用实时定量PCR技术检测BIMmRNA表达的变化;用Western blot检测A3D8处理后磷酸化ERK-1/2的表达变化。结果表明:A3D8能显著抑制HL-60细胞的增殖,抑制效率呈现剂量和时间的量效关系,并可进一步诱导HL-60细胞的早期凋亡,而BCL-2家族成员Bim的表达水平也随时间和浓度的变化而改变,磷酸化ERK-1/2的表达水平明显降低。结论 :CD44单克隆抗体A3D8可通过降低磷酸化ERK-1/2的表达来调节Bim,从而诱导HL-60细胞的增殖抑制和早期凋亡。 This study was aimed to investigate the effects of anti-CD44 mAb A3D8 on proliferation and apoptosis of AML cells, to explore the mechanism of ERK1/2 and Bim in this process. Effect of the anti-CD44 mAb A3D8 on the FIL-60 cell proliferation was assayed with MTT method, the change of mitochondrial transmembrane potential of HL-60 cells was analyzed by flow eytometry. The rnRNA expression of Bim was determined by real-time quantitative RT-PCR. Wersten blot was used to detect the protein expression of p-ERK1/2. The results showed that m_Ab A3D8 could remarkably inhibit the proliferation capacity of the HL-60 cells in a dosage- and time-dependent ways. The mitochondrial transmembrane potential in HL-60 cells treated with A3D8 （3.0 μg/ml） was significantly decreased as compared with the control cells. Furthermore, the mRNA expression of Bim was much higher than that in controls. Expression of the p-ERK was much lower than that of the controls. It is concluded that anti-CD44 mAb A3D8 can inhibit the proliferation and induce the apoptosis of HL-60 cells, mechanism of which is enhancing the expression of Bim via inhibiting p-ERK1/2.
作者 常国强 王建 高伟 王若君 王立洪 金薇娜 蔺亚妮 李华文 庞天翔
机构地区 中国医学科学院北京协和医学院血液学研究所血液病医院实验血液学国家重点实验室
出处 《中国实验血液学杂志》 CAS CSCD 2011年第3期656-660,共5页 Journal of Experimental Hematology
基金 天津市自然科学基金(编号09JCZDJC17300) 高等学校博士学科点专项科研基金(编号20091106110038)
关键词 HL-60细胞 A3D8抗体 P-ERK BIM HL-60 cell A3 D8 antibody p-ERKI/2 Bim
分类号 R733.7 [医药卫生—肿瘤]
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参考文献18

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二级参考文献28

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中国实验血液学杂志
2011年 第3期

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