CAJ | 학술논문

目的探讨细胞分化剂Ⅱ(CDA-Ⅱ)对人类急性早幼粒细胞白血病细胞株HL-60分化的影响及其机制.方法 CDA-Ⅱ作用HL-60后,采用瑞特染色法观察细胞的形态变化；流式细胞术检测CD11b阳性细胞比例；用表达谱芯片检测差异表达基因.结果瑞特染色显示CDA-Ⅱ可诱导HL-60细胞向髓系成熟阶段分化,且呈时间依赖性.HL-60细胞经CDA-Ⅱ处理后CD11b阳性表达率呈时间、浓度依赖性增高.CDA-Ⅱ可引起HL-60细胞基因表达变化,其中表达变化相差2倍以上的基因有113条上调基因及140条下调基因.上调基因主要参与矿物质吸收、补体与凝血系统等6条通路；下调基因主要参与嘧啶代谢、RNA聚合酶、嘌呤代谢等9条通路.结论 CDA-Ⅱ可诱导HL-60细胞基因表达变化及细胞分化,CDA-Ⅱ具有用于诱导分化治疗急性早幼粒细胞白血病的可行性.
목적 탐토세포분화제Ⅱ(CDA-Ⅱ)대인류급성조유립세포백혈병세포주HL-60분화적영향급기궤제.방법 CDA-Ⅱ작용HL-60후,채용서특염색법관찰세포적형태변화；류식세포술검측CD11b양성세포비례；용표체보심편검측차이표체기인.결과 서특염색현시CDA-Ⅱ가유도HL-60세포향수계성숙계단분화,차정시간의뢰성.HL-60세포경CDA-Ⅱ처리후CD11b양성표체솔정시간、농도의뢰성증고.CDA-Ⅱ가인기HL-60세포기인표체변화,기중표체변화상차2배이상적기인유113조상조기인급140조하조기인.상조기인주요삼여광물질흡수、보체여응혈계통등6조통로；하조기인주요삼여밀정대사、RNA취합매、표령대사등9조통로.결론 CDA-Ⅱ가유도HL-60세포기인표체변화급세포분화,CDA-Ⅱ구유용우유도분화치료급성조유립세포백혈병적가행성.
Objective To investigate the effect and mechanism of cell differentiation agent Ⅱ (CDA-Ⅱ) on the differentiation of human acute mycloid leukemia (APL) HL-60 cells.Methods The cell morphology and differentiation was detected by Wright-Giemsa staining,the expression of cell surface differentiation antigen CD11b of HL-60 was detected by flow cytometry,the differentially expressed genes were screened by gene expression profile chip (NimbleGen).Results The result of Wright-Giemsa staining showed that CDA-Ⅱ induced HL-60 differentiation towards mature stages in a time-dependent manner.After treated with CDA-Ⅱ,the percentage of CD11b-positive HL-60 cells significantly increased in a time-and dose-dependent manner.The result of gene expression profiling indicated differentially expressed genes including 113 up-regulation genes and 140 down-regulation genes.The up-regulation expression genes involved in six pathways including mineral absorption,complement and coagulation cascades,down-regulation expression genes involved in nine pathways including pyrimidine metabolism,RNA polymerase,purine metabolism and so on.Conclusion CDA-Ⅱ can induce HL-60 differentiation and make gene differentially expressed.The data provide the feasibility of CDA-Ⅱ in differentiation induction therapy for APL.