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目的:探讨羟基脲(hydroxyurea,Hu)及Hu联合粒系-巨噬系集落刺激因子(granulocyticmacrophagecolony-stimulatingfactor,GM-CSF)对慢性粒细胞白血病(chronicmyelogenousleukemia,CML)细胞株K562细胞生长及凋亡相关基因表达的调节效应。方法:以Hu及Hu联合GM-CSF培养K562细胞,采用逆转录-聚合酶链反应(RT-PCR)来分析培养48小时后bcr-abl、bax、c-myc基因表达水平。结果:Hu显著抑制bcr-abl基因表达,促进bax基因表达,但对c-myc基因表达无影响。GM-CSF可部分桔抗Hu对bcr-abl、bax基因表达的调节效应,显著上调c-myc基因表达水平。结论:除直接细胞毒作用外,Hu可通过下调bcr-abl和上调bax基因表达水平而诱导细胞死亡或凋亡。由于GM-CSF有部分持抗化疗药物的效应,故临床上在采用Hu治疗CML患者的同时,宜慎重使用GM-CSF。
OBJECTIVE: To investigate the effects of hydroxyurea (Hu) and Hu combined with granulocytic macrophage colony-stimulating factor (GM-CSF) on the growth and apoptosis of chronic myelogenous leukemia (CML) cell line K562. The regulatory effect of gene expression. Methods: K562 cells were cultured with Hu and Hu combined with GM-CSF. The expression levels of bcr-abl, bax and c-myc genes were analyzed by reverse transcription-polymerase chain reaction (RT-PCR) for 48 hours. Results: Hu significantly inhibited the expression of bcr-abl gene and promoted the expression of bax gene, but had no effect on the expression of c-myc gene. GM-CSF can partially regulate the expression of bcr-abl and bax genes in citrus against Hu, and significantly up-regulates the expression of c-myc gene. CONCLUSION: In addition to direct cytotoxicity, Hu can induce cell death or apoptosis by down-regulating bcr-abl and up-regulating bax gene expression. Since GM-CSF has some anti-chemotherapeutic effects, it is clinically appropriate to use Hu in the treatment of CML patients, and GM-CSF should be used with caution.