自噬活性调节胶质瘤起始细胞辐射敏感性的体内实验研究  

The enhancement of radio-sensitivity via autophagy induced by rapamycin with glioma-initiating cells in vivo

作　　者：赵江虎[1] 庄文卓[1] 龙林梅[1] 李峰[1] 梁中琴[1] 

机构地区：[1]苏州大学医学部药理学系,苏州215123

出　　处：《辐射研究与辐射工艺学报》2012年第1期37-41,共5页Journal of Radiation Research and Radiation Processing

基　　金：国家自然基金(30873052;81072656);江苏省自然科学基金(BK2010226);江苏省普通高校研究生科研创新计划(CX10B_057Z);苏州大学优秀博士论文选题立项(23320935);国家级大学生创新性实验计划(SG315866)资助

摘　　要：为探讨自噬调节对胶质瘤起始细胞移植瘤辐射敏感性的影响,建立裸小鼠皮下移植瘤模型,测量肿瘤体积大小,比较抑瘤率检测雷帕霉素对移植瘤的辐射增敏作用;建立裸小鼠颅内移植瘤模型,观察裸小鼠生存期,HE染色观察移植瘤的生长。取两种模型中各组肿瘤组织做Western blot,分析自噬相关蛋白LC3表达。结果显示,裸小鼠皮下移植瘤模型中,联合治疗组的肿瘤体积明显小于阴性对照组和单纯辐照组(P>0.05),抑瘤率明显增加(P>0.05);在裸小鼠颅内原位移植瘤模型中,联合治疗组的裸小鼠生存期较阴性对照组和单纯辐照组明显延长,HE染色中可见联合治疗组肿瘤生长局限,与周围正常脑组织界限清楚。Western blot结果显示,两种模型中,联合治疗组中的比值LC3II/LC3I显著增加。研究表明,自噬激动剂雷帕霉素通过激活胶质瘤起始细胞的自噬活性,增加胶质瘤的辐射敏感性。To investigate the effect of rapamycin（RPM） on radio-sensitivity of glioma-initiating cells（GICs） in vivo,GICs were inoculated subcutaneously into the NC nude mice.And an intracranial orthotropic model was utilized for evaluation of radio-sensitivity by use of orthotropic injection.Protein levels of LC3 were analyzed with immunoblotting.It was found that tumor inhibition ratio of RPM＋IR group was higher than that in control group and IR group.Combination treatment of nude mice bearing intracranial GICs glioma xenografts with rapamycin and IR made a significant increment of animal survival compared with control or IR alone group.Western blot assay showed that the rate of LC3 II /LC3-I increased obviously in combination treatment group among two models.As a conclusion,Rapamycin can enhance the radio-sensitivity of glioma-initiating cells by inducing autophagy in vivo.

关 键 词：胶质瘤起始细胞 自噬 辐射增敏 雷帕霉素 体内实验 

分 类 号：R730.264[医药卫生—肿瘤]