131I therapy mediated by sodium/iodide symporter combined with kringle 5 has a synergistic therapeutic effect on glioma.

Abstract

Glioblastoma (GBM) is the most common and most aggressive primary brain tumor; the prognosis of patients with GBM remains poor. The sodium/iodide symporter (NIS) can be used to absorb several isotopes, such as 131I for nuclear medicine imaging and radionuclide therapy. Previously, we found that the early growth response-1 (Egr1) promoter had an 131I radiation positive feedback effect on the NIS gene. Kringle 5 (K5), a kringle domain of plasminogen, induced endothelial cell apoptosis. We investigated the effect of K5 combined with the 131I radiation positive feedback effect (Egr1-NIS) for treating malignant U87 glioma cells using a lentiviral vector. We successfully constructed a stable U87 glioma cell line, U87-K5-Egr1-NIS. The radio-inducible Egr1 promoter induced an 131I radiation positive feedback effect absorbed by NIS. Mediated by 131I, K5 increased glioma cell apoptosis; 131I radiation also increased endothelial cell sensitivity to K5-induced apoptosis. The combined therapy had a synergistic effect on the antitumor efficacy of glioma treatment, not only increasing tumor cell apoptosis but also significantly inhibiting tumor cell proliferation and reducing capillary density in U87 glioma tissues.