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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。
CD44 monoclonal antibody A3D8 can inhibit the proliferation of acute myeloid leukemia (AML) cells and induce its early apoptosis. This study explored the mechanism of action of ERK and BCL-2 family members in this process, providing new methods and new drug targets for the treatment of leukemia. The inhibitory effect of A3D8 on the proliferation of HL-60 cells was detected by MTT assay. The changes of mitochondrial membrane potential of HL-60 cells by A3D8 were detected by flow cytometry. The changes of BIM mRNA expression were detected by real-time quantitative PCR. Post-phosphorylation ERK-1/2 expression changes. The results showed that: A3D8 could significantly inhibit the proliferation of HL-60 cells, the dose-and time-dependent dose-response relationship demonstrated that A3D8 could induce early apoptosis in HL-60 cells, while the expression level of Bim in BCL-2 Time and concentration changes, the expression level of phosphorylated ERK-1/2 decreased significantly. CONCLUSION: A3D8, a monoclonal antibody against CD44, can regulate Bim by decreasing the expression of phosphorylated ERK-1/2, thereby inducing the proliferation inhibition and early apoptosis of HL-60 cells.