异甘草素增加人脑胶质瘤干细胞放射敏感性的实验研究  

Isoliquiritigenin promotes the radiosensitivity of human glioma stem cells

作　　者：林瑜亮 党莹[1] 孙红军[1] 荔志云[1] 

机构地区：[1]兰州军区兰州总医院神经外科,兰州市730050

出　　处：《中国肿瘤临床》2017年第22期1120-1124,共5页Chinese Journal of Clinical Oncology

基　　金：甘肃省重点研发计划(社会发展类)项目(编号:17YFIFA136)资助~~

摘　　要：目的:研究异甘草素对胶质瘤干细胞(glioma stem cells,GSCs)放射敏感性的影响及作用机制。方法:无血清培养法提取SHG44人脑GSCs。检测异甘草素和X射线联合运用下GSCs活性和干细胞球形成情况。检测Notch1信号通路、NF-κB和caspase-3的表达情况。结果:采用10μM异甘草素在8 Gy较高剂量X射线存在的情况下,能够抑制GSCs球的数目和直径(P<0.05)。20μM异甘草素杀伤GSCs的作用明显,且在4、8 Gy的X射线下联合杀伤GSCs的能力依次增强(P<0.05)。异甘草素干作用48 h后Notch1的表达下调(P<0.05)。4 Gy的X射线照射后,分别于6、24 h,异甘草素干预组P-NF-κB表达逐渐增高(P<0.05),而cleaved caspase-3的表达在X射线照射后的24 h开始升高(P<0.05)。结论:异甘草素能够增加GSCs的放射敏感性,抑制Noch1信号通路,上调NF-κB和caspase-3的表达,参与X射线对GSCs的损伤过程。Objective：To investigate the influence of isoliquiritigenin on the radiosensitivity of glioma stem cells and demonstrate the potential underlying mechanism.Methods：Glioma stem cells were isolated from SHG44 human glioma cells by serum-free medium.Cell proliferation abilities were detected after isoliquiritigenin treatment and radiotherapy by using Cell Counting Kit-8.The formation of glioma stem cell spheres was observed using an inverted microscope.The protein expression levels of Notch1 signal pathway,NF-κB,and caspase-3 were examined by Western blot analysis.Results：Isoliquiritigenin（10 μM） inhibited the formation of tumorspheres at 8 Gy radiation（P〈0.05）.Isoliquiritigenin（20 μM） exerted evident growth inhibitory effect on glioma stem cells.Isoliquiritigenin pretreatment combined with 4 or 8 Gy radiation reduced the cell radioresistance significantly（P〈0.05）.The protein expression levels of Notch1 in the isoliquiritigenin and DAPT groups were lower than those of the control at 48 h after isoliquiritigenin treatment（P〈0.05）.The protein expression levels of P-NF-κB began to increase at 6 and 24 h after 4 Gy radiation with isoliquiritigenin pretreatment（P〈0.05）.Isoliquiritigenin pretreatment combined with 4 Gy radiation increased the protein expression level of cleaved caspase-3 at 24 h after radiation compared with that of the isoliquiritigenin treatment alone（P〈0.05）.Conclusion：Isoliquiritigenin may downregulate Notch1 signal pathway and affect different aspects of cell stress and death,including NF-κB-and caspase-3-associated processes,thereby promoting the radiosensitivity of glioma stem cells.

关 键 词：异甘草素 胶质瘤干细胞 放射敏感性 NOTCH1 NF-ΚB CASPASE-3 

分 类 号：R739.41[医药卫生—肿瘤]