下调BMI1表达放射增敏脑胶质瘤干细胞  

Downregulation of BMI1 Induces Glioma Stem Cells Sensitive to Radiation

作　　者：刘志刚[1,2] 付军[1,3] 陶亚岚[1,2] 刘晓梅[1,2] 陈忠平[1,3] 夏云飞[1,2] 

机构地区：[1]华南肿瘤学国家重点实验室,广东广州510060 [2]中山大学肿瘤防治中心放射治疗科/放射生物实验室,广东广州510060 [3]中山大学肿瘤防治中心神经外科/神经肿瘤科,广东广州510060

出　　处：《中国神经肿瘤杂志》2010年第4期233-237,共5页Chinese Journal of Neuro-Oncology

摘　　要：背景与目的:BMI1是维持肿瘤干细胞自我更新的重要因子。本研究主要探讨其与胶质瘤干细胞放射敏感性的关系。方法:采用免疫磁珠分选CD133阳性胶质瘤细胞,低密度单克隆形成神经球。蛋白质印迹检测慢病毒载体携带shBMI1的干扰效果。平板集落形成评估BMI1干扰后放射敏感性。Annexin V免疫荧光染色用于测定细胞凋亡。组蛋白γH2AX灶点形成检测DNA损伤修复。结果:BMI1在胶质瘤干细胞0814中高表达,通过慢病毒携带RNA干扰,能够显著下调BMI1的表达,下调BMI1表达联合放疗能够显著降低脑胶质瘤干细胞集落形成,联合BMI1干扰及放射治疗显著地提高了细胞凋亡比率(P<0.01),并且干扰BMI1后,胶质瘤干细胞0814的DNA损伤修复能力出现显著缺陷。结论:BMI1可望是恶性脑胶质瘤非常有前景的放射治疗增敏靶点。BACKGROUND & OBJECTIVE: BMI1 is essential for maintaining self-renewal of glioma stem cell(GSCs).This study investigated if BMI1 contributes to radioresistance.METHODS: GSCs have been isolated by using CD133 magnetic beads from human glioblastoma specimens and neurospheres were derived from single CD133-positive cell in serum-free medium in vitro.Western blot detected the efficacy of BMI1 interference.Radiosensitization effect was assessed by colony formation assay.Apoptosis cell death was determined by Annexin V staining.And DNA damage repair was evaluated by histone γH2AX foci formation.All statistical analyses and charting were performed using the Sigma-plot software package,version10.0.RESULTS: Down-regulation of BMI1 expression combined with radiotherapy significantly reduced glioma stem cell colony formation,enhanced induction of apoptosis and impaired DNA damage repair systems.CONCLUSION: BMI1 is a promising target for radiation sensitization of malignant glioma.

关 键 词：胶质瘤 BMI1 肿瘤干细胞 放射治疗 

分 类 号：R739.41[医药卫生—肿瘤]