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Tumor Biology

, Volume 33, Issue 5, pp 1607–1618 | Cite as

CpG ODN107 potentiates radiosensitivity of human glioma cells via TLR9-mediated NF-κB activation and NO production

  • Xiaoli Li
  • Dan Liu
  • Xin Liu
  • Weiwei Jiang
  • Weiying Zhou
  • Wei Yan
  • Yanyan Cen
  • Bin Li
  • Guanqun Cao
  • Guofu Ding
  • Xueli Pang
  • Jianguo Sun
  • Jiang Zheng
  • Hong Zhou
Research Article

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 G1 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.

Keywords

CpG ODN107 Glioma Radiosensitivity NO TLR9 Cell cycle arrest 

Abbreviations

CpG ODN

Oligodeoxynucleotides containing unmethylated CG dinucleotides

LPS

Lipopolysacchride

MTT

3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide

NO

Nitric oxide

iNOS

Inducible nitric oxide synthase

NF-κB

Nuclear factor-κB

IR

Irradiation

TLR

Toll-like receptor

IC10

Inhibitor concentration at which 10 % enzyme inhibition occurs

TGD

Tumor growth delay

TVQT

Tumor volumes quadrupling time

SF

Surviving fraction.

Notes

Acknowledgments

Financial support was provided from a major scientific and technological special project for “Significant New Drugs Creation” of China (2009ZX09103-051). Thanks are also due to senior technician Hong Xiao, Technician Xi Wang, and Zhan Jiang in Department of Oncology of Southwest Hospital for technical assistance.

Conflicts of interest

None.

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2012

Authors and Affiliations

  • Xiaoli Li
    • 1
  • Dan Liu
    • 1
  • Xin Liu
    • 2
  • Weiwei Jiang
    • 1
  • Weiying Zhou
    • 1
  • Wei Yan
    • 1
  • Yanyan Cen
    • 1
  • Bin Li
    • 1
  • Guanqun Cao
    • 3
  • Guofu Ding
    • 1
  • Xueli Pang
    • 4
  • Jianguo Sun
    • 5
  • Jiang Zheng
    • 2
  • Hong Zhou
    • 1
  1. 1.Department of Pharmacology, College of PharmacyThe Third Military Medical UniversityChongqingPeople’s Republic of China
  2. 2.Medical Research Center, Southwest HospitalThe Third Military Medical UniversityChongqingPeople’s Republic of China
  3. 3.Company 15th, Students of BrigadeThe Third Military Medical UniversityChongqingChina
  4. 4.Department of Oncology, Southwest HospitalThe Third Military Medical UniversityChongqingChina
  5. 5.Department of Oncology, Xinqiao HospitalThe Third Military Medical UniversityChongqingChina

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