title: CpG ODN107 potentiates radiosensitivity of human glioma cells via TLR9-mediated NF-κB activation and NO production.
abstract: Radiotherapy is a standard treatment for glioma patient with or without surgery; radiosensitizer can increase tumor sensitivity for radiotherapy. Herein, a synthetic oligodeoxynucleotide containing unmethylated CpG dinucleotides (CpG ODN107) as a radiosensitizer was investigated in vitro and in vivo, and the possible mechanisms were studied in vitro. In the present experiments, the human glioma U87 cell line used herein was resistant to 5 Gy of β-ray irradiation. The results showed that 10 μg/ml of CpG ODN107 in combination with irradiation significantly inhibited cell proliferation both in MTT assay and colony formation experiments. Tumor growth was inhibited by CpG ODN107 in combination with local irradiation but not by local irradiation or CpG ODN107 alone in human glioma xenograft model in nude mice. The inhibition ratio of tumor growth produced by CpG ODN107 (1.7, 5, and 15 mg/kg) in combination with irradiation was 27.3, 67.0, and 65.5 %, respectively. Further molecular mechanisms were studied in vitro. The results showed that the expressions of iNOS, NO, TLR9 mRNA, and NF-κB p50/p65 increased in the cells treated with CpG ODN107 in combination with irradiation. CpG ODN107 in combination with irradiation did not induce apoptosis but induced cell cycle arrest at G(1) phase. The said results demonstrated that CpG ODN107 possessed a radiosensitizing effect via TLR9-mediated NF-κB activation and NO production in the tumor cells, leading to cell cycle arrest. Therefore, CpG ODN107 is a potential candidate as radiosensitizer for human glioma.
authors: Department of Pharmacology, College of Pharmacy, The Third Military Medical University, Gaotanyan Street 30, Shapingba District, Chongqing, 400038, People's Republic of China.
authors: Xiaoli
authors: X
authors: Li
authors: Dan
authors: D
authors: Liu
authors: Xin
authors: X
authors: Liu
authors: Weiwei
authors: W
authors: Jiang
authors: Weiying
authors: W
authors: Zhou
authors: Wei
authors: W
authors: Yan
authors: Yanyan
authors: Y
authors: Cen
authors: Bin
authors: B
authors: Li
authors: Guanqun
authors: G
authors: Cao
authors: Guofu
authors: G
authors: Ding
authors: Xueli
authors: X
authors: Pang
authors: Jianguo
authors: J
authors: Sun
authors: Jiang
authors: J
authors: Zheng
authors: Hong
authors: H
authors: Zhou
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism*; D059447:Cell Cycle Checkpoints / Q000187:drug effects / Q000528:radiation effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects / Q000528:radiation effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000528:radiation effects; D005910:Glioma / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D016328:NF-kappa B / Q000378:metabolism*; D009569:Nitric Oxide / Q000096:biosynthesis*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage / Q000494:pharmacology*; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage / Q000494:pharmacology*; D051217:Toll-Like Receptor 9 / Q000235:genetics / Q000378:metabolism*; D047368:Tumor Burden / Q000187:drug effects / Q000528:radiation effects; D023041:Xenograft Model Antitumor Assays
chemical_list: C576997:CpG ODN107; D016328:NF-kappa B; D009838:Oligodeoxyribonucleotides; D011838:Radiation-Sensitizing Agents; D051217:Toll-Like Receptor 9; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II