title: The radiosensitizing effect of CpG ODN107 on human glioma cells is tightly related to its antiangiogenic activity via suppression of HIF-1α/VEGF pathway.
abstract: Malignant glioma displays invasive growth and is difficult to be completely excised; surgery combined with subsequent radiotherapy is a standard treatment for patients. CpG oligodeoxynucleotides (CpG ODN) can enhance radiotherapeutic effect in some tumors. Angiogenesis is crucial for tumor progression and metastasis. Anti-angiogenic strategy thus may be effective for tumor treatment. Herein, the antiangiogenic activity and radiosensitizing effect of CpG ODN107 on glioma were investigated. Our results showed that the growth of glioma cell line U87 was significantly inhibited by CpG ODN107 (10μg/ml) in combination with irradiation (5Gy) in vitro. In orthotopic implantation model of nude mice, the survival rate of mice significantly increased after treatment with CpG ODN107 (0.083mg/kg) in combination with radiotherapy (10Gy) as compared with treatment with local radiotherapy alone. CpG ODN107 in combination with radiotherapy significantly decreased microvessel density (MVD), VEGF level and HIF-1α expression in orthotopic implantation glioma. In conclusion, CpG ODN107 significantly increased the radiosensitivity of U87 human glioma cells in vitro and in vivo. The radiosensitizing effect of CpG ODN 107 is tightly related to its anti-angiogenic activity via suppression of HIF-1α/VEGF pathway.
authors.affiliation: Department of Pharmacology, Third Military Medical University, Chongqing, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Liu
authors.forename: Guanqun
authors.initials: G
authors.lastname: Cao
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Cen
authors.forename: Tao
authors.initials: T
authors.lastname: Liu
authors.forename: Wei
authors.initials: W
authors.lastname: Peng
authors.forename: Jianguo
authors.initials: J
authors.lastname: Sun
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Li
authors.forename: Hong
authors.initials: H
authors.lastname: Zhou
mesh_terms: D020533:Angiogenesis Inhibitors / Q000008:administration & dosage* / Q000494:pharmacology; D000818:Animals; D001932:Brain Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000532:radiotherapy; D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy; D005910:Glioma / Q000098:blood supply / Q000188:drug therapy* / Q000532:radiotherapy; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D008819:Mice, Nude; D055806:Microvessels / Q000187:drug effects* / Q000473:pathology; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000532:radiotherapy; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage* / Q000494:pharmacology; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage* / Q000494:pharmacology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D020533:Angiogenesis Inhibitors; C576997:CpG ODN107; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009838:Oligodeoxyribonucleotides; D011838:Radiation-Sensitizing Agents; D042461:Vascular Endothelial Growth Factor A
keywords: Anti-angiogenic activity; CpG ODN107; HIF-1α; Radiosensitivity; VEGF