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目的探讨酪氨酸激酶抑制剂AG-490对人慢性髓系白血病急变细胞株K562细胞的增殖及凋亡的影响。方法采用MTT法观察AG-490在体外对人慢性髓系白血病急变细胞株K562细胞增殖的影响,光学显微镜下观察AG-490对K562细胞形态的变化,流式细胞术检测AG-490对K562细胞凋亡及细胞周期的影响,逆转录-聚合酶链反应(RT-PCR)及实时荧光定量PCR技术检测AG-490作用后K562细胞bcr/abl融合基因及凋亡相关基因c-myc mRNA的表达水平。结果 AG-490可明显抑制K562细胞的增殖,并随药物作用时间的延长和浓度的增加,抑制作用越明显(P<0.05);AG-490可使细胞周期阻滞于G1期,促使其凋亡(P<0.05)。AG-490作用于K562细胞48 h后bcr/abl融合基因的表达无明显改变(P>0.05),而c-myc的表达水平明显降低(P<0.05)。结论 AG-490可能通过阻断JAK2信号通路而下调c-myc的表达,使K562细胞阻滞于G1期,从而抑制K562细胞增殖,促使其凋亡。
Objective To investigate the effects of tyrosine kinase inhibitor AG-490 on the proliferation and apoptosis of human acute myeloid leukemia K562 cells. Methods MTT assay was used to observe the effect of AG-490 on the proliferation of human acute myeloid leukemia K562 cells in vitro. The morphological changes of K562 cells were observed under light microscope. Flow cytometry was used to detect the effect of AG-490 on K562 cells The effect of AG-490 on the expression of bcr / abl fusion gene and apoptosis related gene c-myc mRNA in K562 cells was detected by reverse transcription-polymerase chain reaction (RT-PCR) and real-time fluorescence quantitative PCR Level. Results AG-490 could significantly inhibit the proliferation of K562 cells. With the prolongation of the action time and concentration of AG-490, the inhibition effect was more obvious (P <0.05). AG-490 could block the cell cycle in G1 phase, Dead (P <0.05). The expression of bcr / abl fusion gene in K562 cells treated with AG-490 for 48 h did not change significantly (P> 0.05), while the expression of c-myc was significantly decreased (P <0.05). Conclusion AG-490 may down-regulate the expression of c-myc by blocking the JAK2 signaling pathway, arresting K562 cells in G1 phase, thereby inhibiting K562 cell proliferation and promoting apoptosis.