FK228抑制EPO介导的人红系前体细胞的增殖与分化

EPO mediated proliferation and differentiation of human erythroid progenitor inhibited by FK228

目的:探讨组蛋白脱乙酰化酶抑制剂FK228在红细胞生成素(EPO)介导的人红系前体细胞增殖与分化中的调节作用。方法:从经粒细胞集落刺激因子动员的肿瘤患者外周血单核细胞中分离CD34+细胞,用含干细胞生长因子(SCF)、EPO或SCF+IL-3及不同浓度FK228的无血清培养基培养7d,分别用抗GPA及抗CD36单克隆抗体(mAb)染色并行流式细胞术检测;将CD34+细胞用含SCF+IL-3的无血清培养基培养7d,分离CD36+GPA-细胞,将细胞用含有EPO+FK228的无血清培养基培养7d,并行细胞计数;将CD36+GPAlow/-细胞用含EPO加或不加FK228的无血清培养基培养,并进行annexin V和PI染色。结果:FK228以一种剂量依赖方式抑制CD36+GPAhigh、CD36+GPAlow和CD36+GPA-细胞的产生;FK228可诱导CD36+GPAhigh和CD36+GPAlow/-细胞在含EPO的培养基中发生细胞凋亡。结论:FK228可抑制EPO介导的人红系前体细胞的增殖与分化。

AIM： To investigate the function of histone deacetylases （HDACs） inhibitor FK228 in the EPO mediated proliferation and differentiation of human erythroid progenitor. METHODS： CD34^＋cells were separated from the granulocyte colony-stimulating factor-mobilized peripheral blood of patients with cancer. They were cultured for 7 days with serum-free medium containing stem cell factor （SCF）, erythropoietin （EPO） or SCF ＋ IL-3 in the presence of escalated dosages of FK228. After immunofluorescent staining with anti-GPA-PE and anti-CD36-FITC, cell count and Flow cytometric analysis were performed; CD34^＋ cells were cultured for 7 days with serum-free medium containing SCF ＋ IL-3 and enriched for CD36^＋ GPA^- cells, which were cultured for 7 days with serum-free medium containing EPO ＋ FK228. Then the cell count was conducted. CD36^＋ GPA^- cells were cultured for 7 days with serum-free medium containing EPO in the presence or absence of FK228 and then they were stained with annexin V and PI. RESULTS： FK228 inhibited the generation of CD36^＋ GPA^high, CD36 ^＋ GPA^low and CD36^＋ GPA^- cells in a dosage-dependent manner. FK228 induced the apoptosis of CD36^＋ GPA^high and CD36^＋ GPA^low/- cells in the presence of EPO. CONCLUSION： FK228 can inhibit the EPO mediated proliferation and differentiation of human erythroid progenitor.