γ-分泌酶抑制剂对胶质瘤细胞株的生长抑制及其放射增敏作用研究  

The cytotoxicity and radiosensitization effects of γ-secretase inhibitor on malignant glioma cell lines and related mechanisms

作　　者：刘锦新[1] 陈奕芝[1] 

机构地区：[1]深圳市龙岗中心医院,广东深圳518116

出　　处：《热带医学杂志》2013年第7期816-819,共4页Journal of Tropical Medicine

基　　金：深圳市龙岗区医疗卫生科技计划项目(YLL2010066);深圳市留深博士后科研资助项目

摘　　要：目的探讨γ-分泌酶抑制剂对U87胶质瘤细胞的增殖抑制及γ-分泌酶抑制剂在放射增敏中的作用。方法 MTT比色法分析γ-分泌酶抑制剂对高表达Notch1的U87细胞的生长抑制作用;流式细胞仪检测其细胞周期分布及细胞凋亡;采用克隆形成实验分析低浓度γ-分泌酶抑制剂对U87细胞放射敏感性的影响。结果经γ-分泌酶抑制剂处理后U87细胞生长被抑制,细胞周期主要停滞在G1期,2.5、5μmol/L的GSI作用U187细胞48h后,其调亡率分别为(3.8±0.58)%和(14.5±0.98)%,均高于Control组的(2.30±0.25)%,差异有统计学意义(P<0.05);低浓度γ-分泌酶抑制剂对U87细胞有显著的放射增敏作用。结论γ-分泌酶抑制剂可阻断Notch信号通路,抑制U87细胞的增殖并诱导凋亡,低浓度γ-分泌酶抑制剂可显著增加U87细胞对放射的敏感性。Objective To investigate the effect of γ-secretase inhibitor on the growth and radiosensitivity of human glioma cell lines U87 and to explore the related mechanisms. Methods Proliferation of U87 cell line was observed by MTF assay. Cell cycle distribution and apopotsis was analyzed by FACS, the colony sorting was used to anzlyzed the effect of radiosensitivity on U87 cell line. Results The growth of U87 cell was inhibited and FACS showed that U87 cell had a prolonged G1 cellcycle and increased apopotsis. Minewhile, colony sorting showed that low-dose of γ-secretase inhibitors can induce radiosensitivity on U87 cell line. Conclusion We present a reliable evidence for clinical glioma treatment, which is γ-secretase inhibitors can dramatically inhibit cell proliferation and induce apoptosis in U87 cell line and lowdose of γ-secretase inhibitors can induce radiosensitivity in U87 cell line.

关 键 词：Γ-分泌酶抑制剂 胶质瘤 细胞周期 放射增敏 

分 类 号：R739.41[医药卫生—肿瘤]