急性髓系白血病细胞热休克蛋白90的表达及其作用机制分析-血液内科学专业论文.docxVIP

II II 4、体外研究结果显示,17-DMAG 能抑制 HL-60 细胞的生长，并且随着药物浓 度的升高、作用时间的延长抑制率明显提高，具有浓度、时间依赖性。 5、对于不同浓度 17-DMAG、48 小时处理的 HL-60 细胞,应用 Western Blot 方法检测细胞中 HSP90 蛋白和 Akt 蛋白的表达，HSP90 蛋白和 Akt 蛋白含量随着 17-DMAG 浓度的升高而出现下降趋势。 结论 1、在正常人、白血病细胞株 HL-60 和急性髓系白血病患者中均有 HSP90mRNA 的表达。在初治患者中有 HSP90 表达显著升高，与正常人比较有显著差异，缓解 期患者表达水平下降，复发时再次升高。 2、HSP90mRNA 表达水平与急性髓系白血病分型无明显关系。 3、HSP90 表达水平可作为急性髓系白血病诊断和病情检测的指标。 4、用特异抑制物（17-DMAG）抑制 HSP90 的表达可显著抑制白血病细胞的增 殖，其作用机制可能是通过抑制 HSP90 而使 Akt 蛋白含量下降，诱导细胞凋亡。 5、HSP90 可作为一个白血病治疗的新靶点。 关键词：白血病；HSP90；HL-60 细胞；17-DMAG ； Akt 蛋白 III III The Expression and Effects of Heat Shock Proteins (HSP90) in the Acute Myeloid Leukemia Cells Abstract Objective: To study the expression of HSP90 in acute myelocytic leukemia cells and its relationship with FAB subtypes and prognosis . To explore the effect of the heat shock protein 90(HSP90) inhibitor on the acute myelocytic leukemia cell lineHL-60 and its related mechanism． Methods: RT-PCR was used to detect the mRNA expression of HSP90 in marrow mononuclear cells from 80 patients with acute myelocytic leukemia (45 male, 35 female), and 10 healthy volunteers (normal controls, NC). The possible correlation between HSP90 mRNA and FAB subtypes, and the prognosis was analyzed. There was an over-expression of HSP90 mRNA in HL-60 cell lines, used as positive controls. The HL-60 cells were treated with different concentrations of 17-DMAG. The (OD) value was detected through MTT assay and the inhibition rate was calculated. The protein level of the signaling molecule Akt and HSP90 were evaluated through Western Blot Results: 1. The high HSP90 mRNA expression was detected in leukemia cell lines tested, with HSP90 mRNA 0.523 in HL-60 cell line .HSP90 mRNA expression in newly diagnosed AML group (the positive rate 100%, the mean level 0.523±0.225) was significantly higher than that in normal control (positive rate:100%，mean level: 0.193±0.054)(P＜0.05). The expression level of HSP90 mRNA( positive rate100%, mean level 0.243±0.087) in complete