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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。
Objective: To investigate the regulatory effect of histone deacetylase inhibitor FK228 on proliferation and differentiation of erythropoietin (EPO) -mediated human erythroid precursor cells. Methods: CD34 + cells were isolated from peripheral blood mononuclear cells (BMMNCs) mobilized from granulocyte-colony stimulating factor-stimulated cells and cultured for 7 days in serum-free media containing stem cell growth factor (SCF), EPO or SCF + IL-3 and different concentrations of FK228 The cells were stained with anti-GPA and anti-CD36 monoclonal antibody (mAb) respectively and detected by flow cytometry. CD34 + cells were cultured with serum-free medium containing SCF + IL-3 for 7 days. CD36 + GPA- Serum-free medium containing EPO + FK228 was cultured for 7 days and counted in parallel. CD36 + GPAlow / - cells were cultured in serum-free medium containing or without FK228 and annexin V and PI staining. Results: FK228 inhibited the production of CD36 + GPAhigh, CD36 + GPAlow and CD36 + GPA-cells in a dose-dependent manner; FK228 induced apoptosis of CD36 + GPAhigh and CD36 + GPAlow / - cells in EPO-containing medium . Conclusion: FK228 can inhibit the proliferation and differentiation of human erythroid precursors induced by EPO.