槲皮素对胶质瘤干/祖细胞的辐射致敏作用及其机制的初步探讨

Autophagy plays a role in promoting radiosensitivity of glioma stem/progenitor cells by quercetin

本研究旨在探讨槲皮素对胶质瘤干/祖细胞辐射敏感性的影响及其机制。用槲皮素(Quercetin,Que)作用于已经建立的胶质瘤干/祖细胞系SU-2,用Western Blot和免疫荧光法检测自噬相关蛋白LC3的变化,以检测SU-2的自噬活性的改变。采用四甲基偶氮唑盐(3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide,MTT)比色法和克隆形成实验比较各处理组对SU-2的增殖抑制作用;应用Annexin V-FITC/PI流式细胞术检测不同因素处理SU-2后细胞凋亡情况的改变。实验结果表明:用槲皮素预先处理胶质瘤干/祖细胞系SU-2再辐照组较单纯辐照组的细胞增殖率降低(p<0.05),克隆形成率明显降低(p<0.05),细胞凋亡率显著增加(p<0.05)。这些结果提示,胶质瘤干/祖细胞的基础自噬活性很低,经槲皮素处理后,再经X线照射,胶质瘤干/祖细胞的自噬活性提高,辐射敏感性明显增加。

To investigate the effect of quercetin on glioma stem/progenitor cells （GSPCs） sensitivity to radiation, GSPCs were exposed to quercetin and IR. The changes in protein levels of LC3 in GSPCs with various treatments were confirmed by the immunoblotting analysis and immunofluorescence analysis. Growth inhibition of GSPCs was assessed with methylthiazolyl tetrazolium （MTT） and cell viability assay. Amaexin V-FITC/PI staining was used to study the treatment effects on apoptosis. The results show that cells previously treated with quercetin and IR gener- ated a decreased number of colonies as compared to untreated cells, and apoptosis level in GSPCs was significantly increased by the combined treatment with quercetin and IR. These suggest that activating autophagy may abrogate the resistance of GSPCs to radiation and could lead to the development of novel therapeutic approaches for the treatment of glioblastomas.