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目的 :探讨新的药物协同 ATRA诱导早幼粒白血病细胞分化作用 ,降低临床 ATRA剂量 ,提高ATRA疗效。方法 :NB4细胞株为实验模型 ,采用细胞生物学研究方法 ,体外研究 IFNγ、TNF和 G- CSF各结合ATRA对 NB4细胞增殖和分化的作用。结果 :在诱导分化和抑制白血病克隆增殖中 ,IFNγ和 TNF具协同作用 ,以IFNγ作用最明显 ,在 ATRA浓度为 10 - 8mol/ L 时 ,比较各细胞因子联合 ATRA对 NB4细胞作用后 NBT的变化 ,发现联合 IFNγ组 NBT仍达 92 % ,高于其它各组 (P<0 .0 1) ,细胞周期变化 :联合 IFNγ作用后使 G0 / G1 期积聚最明显 ,由对照的 5 0 .5 %增至 86 .2 % ,半固体克隆增殖抑制实验显示 ,ATRA与 IFNγ联合用药组具明显抑制 NB4细胞克隆增殖活性作用。结论 :细胞因子 IFNγ与 ATRA联合具较强协同诱导 NB4细胞分化和抑制克隆增殖作用 ,这对临床联合 IFNγ诱导早幼粒白血病分化治疗提高 ATRA疗效有一定价值。
Objective: To explore the new drug-synergic ATRA-induced promyelocytic leukemia cell differentiation, reduce clinical ATRA dose and improve the efficacy of ATRA. Methods: The NB4 cell line was used as an experimental model. The effects of IFNγ, TNF and G-CSF in combination with ATRA on the proliferation and differentiation of NB4 cells were studied in vitro by cell biology method. Results: IFNγ and TNF had a synergistic effect on differentiation and inhibition of leukemic clonal proliferation, with IFNγ as the most obvious effect. When the ATRA concentration was 10 - 8mol / L, the changes of NBT after the combination of cytokines and ATRA were compared , Found that NBT still reached 92% in the combined IFNγ group, which was higher than the other groups (P <0.01). The cell cycle changes: the combination of IFNγ and G0 / G1 phase accumulation was the most obvious, To 86.2%. Experiments on the inhibition of proliferation of semi-solid clones showed that the combination of ATRA and IFNγ significantly inhibited the proliferation of NB4 cells. CONCLUSION: The combination of cytokine IFNγ and ATRA has a strong synergistic effect in inducing the differentiation of NB4 cells and inhibiting the proliferation of clones. It is of great value in clinical treatment of IFNγ-induced differentiation of promyelocytic leukemia and improvement of ATRA efficacy.