Genistein inhibits radiation-induced invasion and migration of glioblastoma cells by blocking the DNA-PKcs/Akt2/Rac1 signaling pathway

Highlights: • X-ray irradiation enhances the invasion and migration of DNA-PKcs-positive but not DNA-PKcs-negative GBM cells. • X-ray irradiation activate the DNA-PKcs/Akt2/Rac1 signaling pathway, which contributes to GBM malignant progression via aggravating GBM cell invasive potential. • Genistein could specifically bind to DNA-PKcs and block the DNA-PKcs/Akt2/Rac1 pathway. • DNA-PKcs is not only one of the key proteins of DSB repair, but also a reliable biomarker for predicting the radiation-induced invasion and migration of GBM cells. Radiotherapy is the most important therapeutic measure against glioblastoma multiforme (GBM), which is regarded as the most common and highly lethal type of brain cancer. Nevertheless, most relapses originate in the close vicinity of the irradiated target volume. Genistein is a natural product that can suppress the invasive potential of cancer cells. In this study, DNA-dependent protein kinase catalytic subunit (DNA-PKcs)-proficient and -deficient GBM cells were selected for in vitro and in vivo studies to investigate the inhibiting effects of genistein on radiation-induced invasion and migration and the corresponding mechanism.