title: 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.
authors.affiliation: Department of Nuclear Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, P.R. China.
authors.forename: Shuo
authors.initials: S
authors.lastname: Shi
authors.affiliation: Department of Nuclear Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, P.R. China.
authors.forename: Min
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Nuclear Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, P.R. China.
authors.forename: Rui
authors.initials: R
authors.lastname: Guo
authors.affiliation: Department of Nuclear Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, P.R. China.
authors.forename: Miao
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Nuclear Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, P.R. China.
authors.forename: Jiajia
authors.initials: J
authors.lastname: Hu
authors.affiliation: Department of Nuclear Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, P.R. China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Xi
authors.affiliation: Department of Nuclear Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, P.R. China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Miao
authors.affiliation: Department of Nuclear Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, P.R. China.
authors.forename: Biao
authors.initials: B
authors.lastname: Li
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D045744:Cell Line, Tumor; D051766:Early Growth Response Protein 1 / Q000235:genetics / Q000494:pharmacology; D042783:Endothelial Cells / Q000187:drug effects; D015316:Genetic Therapy / Q000379:methods*; D005910:Glioma / Q000473:pathology*; D006801:Humans; D007457:Iodine Radioisotopes / Q000494:pharmacology; D018082:Kringles; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010958:Plasminogen / Q000378:metabolism; D027981:Symporters / Q000235:genetics*; D015899:Tomography, Emission-Computed, Single-Photon; D014162:Transfection; D023041:Xenograft Model Antitumor Assays; D000099209:Sodium-Iodide Symporters
chemical_list: D000970:Antineoplastic Agents; D051766:Early Growth Response Protein 1; D007457:Iodine Radioisotopes; D010958:Plasminogen; D027981:Symporters; D000099209:Sodium-Iodide Symporters; C497325:EGR1 protein, human