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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 inhibitory effects of γ-secretase inhibitor on the proliferation of U87 glioma cells and the role of γ-secretase inhibitors in radiosensitization. Methods MTT assay was used to analyze the inhibitory effect of γ-secretase inhibitors on the growth of U87 cells with high expression of Notch1. The cell cycle distribution and apoptosis were detected by flow cytometry. The inhibitory effect of low-concentration γ-secretase On the radiosensitivity of U87 cells. Results The growth of U87 cells was inhibited by γ-secretase inhibitor and the cell cycle was mainly arrested in G1 phase. The apoptotic rates of U87 cells treated with 2.5 and 5μmol / L GSI for 48 hours were (3.8 ± 0.58)% and (14.5 ± 0.98)%, respectively, which were significantly higher than those in Control group (2.30 ± 0.25)% (P <0.05). Low concentration of γ-secretase inhibitor had significant radiosensitization effect on U87 cells. Conclusion γ-secretase inhibitors can block the Notch signaling pathway, inhibit the proliferation of U87 cells and induce apoptosis. Low concentrations of γ-secretase inhibitors can significantly increase the sensitivity of U87 cells to radiation.