Hu联合GM-CSF对K562细胞生长-凋亡相关基因表达的影响

Influence of hydroxyurea combined with granulocytic macrophage colony-stimulating factor on growth and apoptosis-related oncogene expressions in K562 cells

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 regulatory effects of hydroxyurea (Hu) and Hu combined with granulocytic macrophage colony-stimulating factor (GM-CSF) on growth and apoptosis-related oncogene expressions in K562 cells.Methods: K562 cells were incubated with Hu or with Hu and GM-CSF collectively. The levels of bcr-abl, bax, c-myc gene expression in the cells following 48 hours culture were analysed by using RT-PCR technique. Results: Hu singificantly suppressed the expression of bcr-abl chimeric gene, and sharply accelerated bax gene expression, but did not affect c-myc gene expression. GM-CSF was able to partially inhibit the regulatory effects of Hu on bcr-abl and bax gene expression, and also significantly upregulated the level of c-myc gene expression. Conclusion: In addition to the direct cytotoxicity, Hu can downregulate the level of bcr-abl chimeric gene expression and upregulate the level of bax gene expression. GM-CSF is capable of enhancing the expression of c-myc gene relating to cell proliferation. GM-CSF should be used cautiously when patients with CML were treated by chemotherapy drugs.