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目的:旨在了解不同预激方案作用于急性髓系白血病(acute myeloid leukemia,AML)细胞株HL-60和急性单核细胞白血病(acute monocytic leukemia,AMOL)细胞株U937的体外效应及其机制。方法:设置对照组(未给予药物处理),阿糖胞苷(cytosine arabinoside,Ara-C)、阿克拉霉素(aclarubicin,Acla)和米托蒽醌(mitoxantrone,Mito)单药组,Ara-C联合Acla组以及Mito联合Ara-C的双药联合组,粒细胞集落刺激因子(granulocyte-colony stimulating factor,G-SCF)预激联合Ara-C和Acla(CAG方案)以及G-CSF预激联合Mito和Ara-C(MAG方案)的三药联合组。药物处理各组细胞24和48h后,观察细胞学形态;采用CCK-8法检测各组2种白血病细胞的生长抑制率;FCM检测各组的细胞凋亡率和细胞分化抗原CD11b的表达率;应用FCM检测与细胞凋亡相关的线粒体膜电位(JC-1法)及caspase-3活性的变化。结果:CAG和MAG方案作用48h后,HL-60和U937细胞形态学变化表现为凋亡小体明显增多;各组药物作用48h后,HL-60和U937细胞的生长均受到抑制,三药联合组的细胞存活率明显下降,并呈时间依赖效应。除Ara-C单药组外,其余各组U937细胞的凋亡率均高于HL-60细胞;各组之间细胞分化抗原CD11b的表达率差异无统计学意义。药物作用后,HL-60和U937细胞线粒体膜电位降低,且三药联合组明显高于单药组和对照组(P<0.05);三药联合组和单药组的caspase-3荧光强度较对照组显著增强(P<0.05)。结论:CAG和MAG方案主要通过诱导白血病细胞凋亡而发挥治疗效应,其作用机制可能与降低线粒体膜电位继而激活caspase-3从而诱导白血病细胞凋亡有关。
AIM: To investigate the in vitro effects and mechanisms of different pre-shock regimens on acute myeloid leukemia (AML) cell line HL-60 and acute monocytic leukemia (AMOL) cell line U937. Methods: The control group (no drug treatment), cytosine arabinoside (Ara-C), aclaubicin (Acla) and mitoxantrone (Mito) C combined with Acla group and Mito combined with Ara-C, pre-excitation of granulocyte-colony stimulating factor (G-SCF) combined with Ara-C and Acla (CAG regimen) Combination of Mito and Ara-C (MAG regimen) triple-drug group. After 24 and 48 hours of drug treatment, the cytological morphology was observed. The growth inhibition rate of two kinds of leukemia cells in each group was detected by CCK-8 method. The apoptosis rate and the expression rate of CD11b in each group were detected by FCM. The changes of mitochondrial membrane potential (JC-1) and caspase-3 activity related to apoptosis were detected by FCM. RESULTS: After treated with CAG and MAG for 48h, the morphological changes of HL-60 and U937 cells were markedly increased by apoptotic bodies. The growth of HL-60 and U937 cells was inhibited after 48h treatment, Group of cell viability decreased significantly, and showed a time-dependent effect. The apoptosis rates of U937 cells in all the groups except Ara-C monotherapy group were higher than those in HL-60 cells. There was no significant difference in the expression rate of CD11b between groups. After drug treatment, the mitochondrial membrane potential of HL-60 and U937 cells decreased, and the three drug combination group was significantly higher than the single drug group and the control group (P <0.05). The fluorescence intensity of caspase-3 in the three drug combination group and the single drug group was The control group increased significantly (P <0.05). Conclusion: The CAG and MAG regimens play a therapeutic effect mainly by inducing apoptosis of leukemia cells, and its mechanism may be related to the decrease of mitochondrial membrane potential and the activation of caspase-3 to induce apoptosis of leukemia cells.