蓝萼甲素对急性髓系白血病U937细胞增殖、凋亡、自噬及SIRT1/FoxO1信号通路的影响  

Effects of glaucocalyxin A on proliferation,apoptosis,autophagy and SIRT1/FoxO1 signaling pathway of acute myeloid leukemia U937 cells

作　　者：卢婷[1] 陈会欣[1] 熊晶[1] 何静[1] LU Ting;CHEN Huixin;XIONG Jing;HE Jing(Department of Blood Transfusion,Wuhan First Hospital,Wuhan 430022,China)

机构地区：[1]武汉市第一医院输血科,湖北武汉430022

出　　处：《陕西医学杂志》2023年第8期969-972,986,共5页Shaanxi Medical Journal

基　　金：湖北省卫生健康委员会科研立项课题(WJ2021M018)。

摘　　要：目的:探究蓝萼甲素对急性髓系白血病(AML)U937细胞增殖、凋亡、自噬及沉默信息调节因子1(SIRT1)/叉头框转录因子O1(FoxO1)信号通路的影响。方法:体外培养AML U937细胞,取培养至对数生长期的U937细胞分为对照组(常规培养U937细胞)、三氧化二砷组(在含U937细胞的培养基中加入2μmol/L的三氧化二砷)、蓝萼甲素低(在含U937细胞的培养基中加入2μmol/L蓝萼甲素)、高(在含U937细胞的培养基中加入4μmol/L蓝萼甲素)浓度组,继续培养48 h后。四甲基偶氮唑蓝法检测U937细胞增殖率,流式细胞术检测U937细胞凋亡率,单丹磺酰尸胺荧光染色观察U937细胞自噬小体数量,荧光定量PCR法检测U937细胞SIRT1、FoxO1 mRNA表达水平,蛋白印迹法检测U937细胞SIRT1、FoxO1蛋白表达水平。结果:与对照组相比,三氧化二砷组、蓝萼甲素低、高浓度组U937细胞增殖率显著降低(均P<0.05),凋亡率、自噬小体数量、SIRT1、FoxO1 mRNA和蛋白表达水平显著升高(均P<0.05);与三氧化二砷组相比,蓝萼甲素低、高浓度组U937细胞增殖率显著升高(均P<0.05),凋亡率、自噬小体数量、SIRT1、FoxO1 mRNA和蛋白表达水平显著降低(均P<0.05);与蓝萼甲素低浓度组相比,蓝萼甲素高浓度组U937细胞增殖率显著降低(P<0.05),凋亡率、自噬小体数量、SIRT1、FoxO1 mRNA和蛋白表达水平显著升高(均P<0.05)。结论:蓝萼甲素能抑制U937细胞的增殖,促进其凋亡和自噬,其机制可能与激活SIRT1/FoxO1信号通路有关。Objective:To explore the effects of glaucocalyxin A on proliferation,apoptosis,autophagy and silent information regulator 1(SIRT1)/forkhead transcription factor O1(FoxO1)signaling pathway of acute myeloid leukemia(AML)U937 cells.Methods:AML U937 cells were cultured in vitro.U937 cells cultured to logarithmic growth phase were divided into control group(conventional culture U937 cells),arsenic trioxide group(U937 cells were added with 2μmol/L arsenic trioxide),glaucocalyxin A low concentration group(U937 cells were added with 2μmol/L glaucocalyxin A),glaucocalyxin A high concentration group(U937 cells were added with 4μmol/L glaucocalyxin A),and continued to culture for 48 hours.The proliferation rate of U937 cells was determined by methyl thiazolyl tetrazolium assay,the apoptosis rate of U937 cells was detected by flow cytometry,the number of autophagosomes in U937 cells was observed by fluorescence staining with montane sulfonyl cademide,the mRNA levels of SIRT1 and FoxO1 in U937 cells were detected by fluorescence quantitative PCR,and Western blot was used to detect the protein levels of SIRT1 and FoxO1 in U937 cells.Results:Compared with control group,the proliferation rate of U937 cells in arsenic trioxide group,glaucocalyxin A low and high concentration groups was significantly decreased(all P<0.05),apoptosis rate,autophagosome number,SIRT1,FoxO1 mRNA and protein levels were significantly increased(all P<0.05).Compared with arsenic trioxide group,the proliferation rate of U937 cells in glaucocalyxin A low and high concentration groups was significantly increased(all P<0.05),apoptosis rate,autophagosome number,SIRT1,FoxO1 mRNA and protein levels were significantly decreased(all P<0.05).Compared with glaucocalyxin A low concentration group,the proliferation rate of U937 cells in glaucocalyxin A high concentration group was significantly decreased(P<0.05),apoptosis rate,autophagosome number,SIRT1,FoxO1 mRNA and protein levels were significantly increased(all P<0.05).Conclusion:Glaucocalyxin A can inhibit the

关 键 词：蓝萼甲素 急性髓系白血病U937细胞 沉默信息调节因子1/叉头框转录因子O1信号通路 细胞增殖 细胞凋亡 自噬 

分 类 号：R733.71[医药卫生—肿瘤]