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.