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

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。

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

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.