尼克酰胺通过SIRT1/PGC-1α/HIF2α信号途径介导白血病细胞HL-60糖酵解代谢的作用及机制  

Effect of nicotinamide regulating glycolysis metabolism on leukemic cell HL-60 through SIRT1/PGC-1 alpha/HIF2 alpha pathway

作　　者：刘苗[1] 周攀 李姣姣 姜毅[1] LIU Miao;ZHOU Pan;LI Jiaojiao;JIANG Yi(Dept. of Paediatrics,Renmin Hospital of Wuhan University,Wuhan 430060,Hubei,China;Hubei Medical Devices Quality Supervision and Test Institute,Wuhan 430075,Hubei,China)

机构地区：[1]武汉大学人民医院儿科,湖北武汉430060 [2]湖北省医疗器械质量监督检验研究院,湖北武汉430075

出　　处：《武汉大学学报（医学版）》2019年第1期17-21,共5页Medical Journal of Wuhan University

基　　金：湖北省自然科学基金资助项目(编号:2014CFB395)

摘　　要：目的:探讨尼克酰胺对人慢性髓系白血病细胞HL-60糖酵解代谢途径的影响,以及SIRT1/PGC-1α/HIF2α信号通路在上述过程中的作用。方法:HL-60细胞培养,葡萄糖消耗实验检测白血病细胞糖酵解活性;流式细胞术检测细胞凋亡,RT-PCR和WesternBlot方法检测SIRT1、PGC-1α、HIF2α基因的表达。结果:尼克酰胺能明显抑制白血病细胞HL-60的糖酵解活性和诱导细胞凋亡,此作用呈时间依赖性和浓度依赖性。SIRT1、PGC-1α和HIF2α基因在白血病细胞HL-60均有基础表达,10μmol/L尼克酰胺对HL-60细胞干预24h后,3个基因的mRNA和蛋白表达水平均明显下调(P<0.05)。结论:尼克酰胺能抑制白血病细胞HL-60的糖酵解活性,诱导细胞凋亡,其机制可能与尼克酰胺调节的SIRT1/PGC-1α/HIF2α信号通路有关。Objective: To investigate the effect of nicotinamide regulating the glycolysis metabolism on leukemia cell line HL-60, and explore the role of SIRT1/PGC-1α/HIF2α signaling pathway in this process.Methods: HL-60 cells were incubated. The glycolytic rates of HL-60 were investigated by glucose consumption assay. The apoptosis was detected by flow cytometry. The mRNA and protein expressions of SIRT1, PGC-1α, and HIF2α were detected by RT-PCR and Western Blot method. Re.sults: The results indicated that nicotinamide could inhibit the glycolytic activity and induce the apoptosis in HL-60 cells; this effect was in time-dependent and concentration-dependent way. There was basal expression of SIRT1, PGC-1α and HIF2α genes in the control group. When treated with 10 μmol/L nicotinamide after 24 h, it showed that the mRNA and protein expressions of SIRT1, PGC-1α, and HIF2α were down-regulated most obviously. Conclusion: Nicotinamide can inhibit the glycolytic activity and induce the apoptosis in HL-60 cell, and the mechanism may be associated with the SIRT1/PGC-1α/HIF2α signal pathway.

关 键 词：尼克酰胺 白血病 糖酵解活性 SIRT1/PGC-1α/HIF2α通路 

分 类 号：R733[医药卫生—肿瘤]