Isoliquiritigenin promotes the radiosensitivity of human glioma stem cells / 中国肿瘤临床

ABSTRACT

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 (10μM) inhibited the formation of tumorspheres at 8 Gy radiation (P<0.05). Isoliquiritigenin (20μM) exerted evident growth inhibitory effect on glioma stem cells. Isoliquiritigenin pre-treatment 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.