芹菜素对U937细胞增殖凋亡及SALL4基因和Wnt/β-catenin信号通路的影响  

Effects of apigenin on proliferation and apoptosis of U937 cells as well as on SALL4 gene and Wnt /β-catenin signaling pathway

作　　者：刘江华[1] 戴碧涛[1] 张妮[1] 梁绍燕 于洁[1] 

机构地区：[1]重庆医科大学附属儿童医院血液肿瘤科、儿童发育疾病研究教育部重点实验室儿科学重庆市重点实验室、儿科学重庆市重点实验室、重庆市儿童发育重大疾病诊治与预防国际科技合作基地,重庆400014

出　　处：《中成药》2014年第7期1341-1346,共6页Chinese Traditional Patent Medicine

基　　金：重庆市卫生局2011年医学科研项目基金资助项目(2011-2-208);重庆市卫生局医学科学技术研究重点资助项目(2010-1-42)

摘　　要：目的探讨芹菜素对人U937细胞株增殖和凋亡,以及对该细胞株SALL4基因和Wnt/β-catenin信号通路下游靶基因c-Myc和CCND1表达的影响。方法以不同浓度芹菜素处理对数生长期的U937细胞,倒置显微镜观察细胞形态;CCK-8法检测细胞的增殖活力;流式细胞术检测细胞周期和凋亡;实时荧光定量PCR检测SALL4、c-Myc、和CCND1 mRNA表达水平;Western blot检测SALL4、Bcl-2、Caspase-3蛋白表达水平。结果与对照组相比,芹菜素处理组细胞碎片增多;细胞增殖受抑制,呈时间和剂量依赖性(P<0.05);G2/M期细胞比例增加(P<0.05);凋亡率增加(P<0.05)。芹菜素处理36 h后,U937细胞的SALL4、c-Myc、和CCND1 mRNA表达下调,SALL4和Bcl-2蛋白表达降低,Caspase-3蛋白表达增加,与对照组相比,差异有统计学意义(P<0.05)。结论芹菜素对U937细胞有抑制增殖诱导凋亡的作用,其机制可能与下调SALL4和Bcl-2,活化Caspase-3,阻断Wnt/β-catenin信号通路有关。AIM To investigate the effect of apigenin on the proliferation and apoptosis of U937 cells as well as on the expression of SALL4 gene and c-Myc,CCND1 gene downstream in Wnt /β-catenin signaling pathway.METHODS U937 cells were cultured with different concentrations of apigenin（ 0,20,40,60 μmol /L） and the cell morphology was observed under an inverted microscope. The proliferation activity was evaluated by CCK-8.The cell cycle and apoptosis were determined by flow cytometry. The mRNA expression of SALL4,c-Myc,and CCND1 detected by real-time PCR. The protein expression of SALL4,Bcl-2,and Caspase-3 analyzed by Western blot. RESULTS Compared with the control group,the apigenin treatment groups showed more cell debris. Cell proliferation was inhibited in a time- and does-dependent manner（ P〈 0. 05）. The cell ratio in G2/M and cell apoptosis increased（ P〈 0. 05）. After being cultured with different concentrations of apigenin for 36 h,the mRNA expression of SALL4,c-Myc,and CCND1 down-regulated. The protein expression of SALL4 and Bcl-2 decreased while that of Caspase-3 increased. CONCLUSION Apigenin can inhibit the proliferation and induce apoptosis of U937 cells. The mechanism is possibly related to the downregulation of SALL4 and Bcl-2 and upregulation of Caspase-3,as well as blocking the Wnt /β-catenin signaling pathway.

关 键 词：芹菜素 U937细胞 增殖 凋亡 SALL4基因 WNT/Β-CATENIN信号通路 

分 类 号：R285[医药卫生—中药学]