三氧化二砷诱导人脑胶质瘤干祖细胞凋亡及其机制  

Mechanisms of Apoptosis Induced by Arsenic Trioxide in Human glioma stem cells

作　　者：张祖斌[1,2] 蒋小岗[1,2] 梁中琴[1,2] 周文轩[2] 郭次仪[2] 顾振纶[1,2] 

机构地区：[1]苏州大学医学部药理学系,江苏苏州215123 [2]苏州中药研究所,江苏苏州215007

出　　处：《苏州大学学报（医学版）》2011年第2期196-200,共5页Suzhou University Journal of Medical Science

基　　金：香港保健协会科研基金资助项目(HK20070901)

摘　　要：目的研究三氧化二砷(As2O3)对人脑胶质瘤干祖细胞增殖和周期的影响及其相关分子表达。方法采用四甲基偶氮唑盐(MTT)法测定As2O3对人脑胶质瘤干祖细胞抑制率,流式细胞术检测As2O3对该细胞凋亡和周期的影响,透射电镜观察细胞形态学变化,Western blot和RT-PCR检测Fas、FasL和p53变化。结果 As2O3可明显抑制人脑胶质瘤干祖细胞的增殖,且呈一定的时间剂量依赖关系(P<0.05);此外,人脑胶质瘤干祖细胞周期G1期细胞的比例增加,S期和G2/M期细胞的比例减少;通过形态学观察发现,随着As2O3剂量的增加,镜下凋亡细胞比例逐渐增加,凋亡小体的数量增加;Western blot检测发现,FasL表达上调,p53下调(P<0.05)。结论 As2O3对人脑胶质瘤干祖细胞具有抑制增殖和诱导凋亡作用,其机制可能与上调FasL和下调p53表达相关。Objective To study the apoptosis effects of arsenic trioxide（As2O3） on human glioma stem cells and the involved mechanisms.Methods Cell proliferation of As2O3 on human glioma stem cells was evaluated by MTT assay.The morphological changes were observed by an electron microscope.Cell cycle and apoptosis rate were analysed by flow cytometry（FCM）.The expression of Fas,FasL and p53 involved in the effects of As2O3 on human glioma stem cells was studied by RT-PCR and Western blot.Results MTT assay showed that As2O3 has a anti-proliferation effect on human glioma stem cells in a time-dependant and dose-dependant manner.Morphological changes of apoptosis about cytoplasm vacuolar degeneration and nuclear condensation were observed by electron microscope in As2O3-treated cells.The results of FCM represented the presence of apoptotic peak.Cells were treated with 6μmol/L As2O3 for 24h,48 h and 72h,the apoptosis rate was increased,and the cell cycle was arrested at G1 phase in a time—dependant manner.The expression of FasL was up,and the expression of p53 was down.Conclusion As2O3shows inhibit proliferation and induce apoptosis in human glioma stem cells.The mechanism may be related to up-regulate FasL and down-regulate p53 expression.

关 键 词：三氧化二砷 凋亡 细胞增殖周期 胶质瘤干细胞 FAS/FASL p53 

分 类 号：R730.264[医药卫生—肿瘤]