Radioactive 125I seeds inhibit cell growth and epithelial-mesenchymal transition in human glioblastoma multiforme via a ROS-mediated signaling pathway

Background: Glioblastoma multiforme (GBM) is the most common primary central nervous system neoplasm in adults. Radioactive I-125 seed implantation has been widely applied in the treatment of cancers. Moreover, previous clinical trials have confirmed that I-125 seeds treatment was an effective therapy in GBM. We sought to investigate the effect of I-125 seed on GBM cell growth and Epithelial-mesenchymal transition (EMT). Methods: Cells were exposed to irradiation at different doses. Colony-formation assay, EdU assay, cell cycle analysis, and TUNEL assay were preformed to investigate the radiation sensitivity. The effects of I-125 seeds irradiation on EMT were measured by transwell, Boyden and wound-healing assays. The levels of reactive oxygen species (ROS) were measured by DCF-DA assay. Moreover, the radiation sensitivity and EMT were investigated with or without pretreatment with glutathione. Additionally, nude mice with tumors were measured after treated with radiation. Results: Radioactive I-125 seeds are more effective than X-ray irradiation in inhibiting GBM cell growth. Moreover, EMT was effectively inhibited by I-125 seed irradiation. A mechanism study indicated that GBM cell growth and EMT inhibition were induced by I-125 seeds with the involvement of a ROS-mediated signaling pathway. Conclusions: Radioactive I-125 seeds exhibit novel anticancer activity via a ROS-mediated signaling pathway. These findings have clinical implications for the treatment of patients with GBM by I-125 seeds.