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[摘要]
目的: 探讨γ-干扰素(IFN-γ)对白血病细胞Fas/FasL表达的调控及凋亡的影响。 方法: 应用免疫组织化学方法、TUNEL测凋亡法、细胞培养技术,检测人髓系白血病细胞株HL 60及临床髓系白血病患者单个核细胞的Fas的表达及相关功能,并研究γ-干扰素对之的影响。结果: 白血病细胞表达Fas蛋白较正常骨髓细胞低,并能致共同培养的Jurkat细胞发生凋亡;而IFN-γ能提高其Fas蛋白的表达(P<0.01),且调节作用具有时间、剂量依赖性,并有下调白血病细胞致Jurkat细胞凋亡的能力,且能够增强白血病细胞对Fas途径介导的凋亡敏感性及增强对化疗药物阿糖胞苷的敏感性。结论: IFN-γ能通过对白血病细胞Fas/FasL系统的调控以防止其逃避免疫监视,并能增强白血病细胞对以Fas/FasL为靶标的化疗药物的敏感性。
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[Abstract]
Objective: To investigate the regulatory effect of interferon-γ on the expression of Fas/FasL and the apoptosis of leukemic cells. Methods: The expression of Fas and its function in human acute leukemic cell line HL-60 and in bone marrow mononuclear cells (BMMNC) of patients with acute myeloid leukemia (AML) were studied by immunohistochemical method, TUNEL method, and cell culture technique. The regulatory effect of interferon-γ on them was also investigated. Results: Compared with BMMNC of normal human, leukemic cells had an obviously decreased expression of Fas and induced apoptosis of Jurkat cells. It was found that interferon-γ up-regulated the expression of Fas in a time- and dose-dependent manner(P<0.01). Meanwhile, interferon-γ inhibited Jurkat cells apoptosis induced by leukemic cells, increased the Fas-mediated apoptosis of leukemic cells, and increased the sensitivity of leukemic cells to chemotherapy agents.Conclusion: Interferon-γ can prevent the immune escape of leukemic cells via regulating the Fas/FasL system and increase the sensitivity of leukemic cells to the chemotherapy drugs targeting Fas/FasL system.
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