Enhancement of radiosensitivity by a unique novel NF-B inhibitor, DHMEQ, in prostate cancer

N. Kozakai, Eiji Kikuchi, M. Hasegawa, E. Suzuki, H. Ide, A. Miyajima, Y. Horiguchi, J. Nakashima, K. Umezawa, Naoyuki Shigematsu, Mototsugu Oya

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Background: Inducible activation of nuclear factor (NF)-B is one of the principal mechanisms through which resistant prostate cancer cells are protected from radiotherapy. We hypothesised that inactivation of inducible NF-B with a novel NF-B inhibitor, DHMEQ, would increase the therapeutic effects of radiotherapy.Methods:PC-3 and LNCaP cells were exposed to irradiation and/or DHMEQ. Cell viability, cell cycle analysis, western blotting assay, and NF-B activity were measured. The antitumour effect of irradiation combined with DHMEQ in vivo was also assessed.Results:The combination of DHMEQ with irradiation resulted in cell growth inhibition and G2/M arrest relative to treatment with irradiation alone. Inducible NF-B activity by irradiation was inhibited by DHMEQ treatment. The expression of p53 and p21 in LNCaP, and of 14-3-3 in PC-3 cells, was increased in the combination treatment. In the in vivo study, 64 days after the start of treatment, tumour size was 85.1%, 77.1%, and 64.7% smaller in the combination treatment group than that of the untreated control, DHMEQ-treated alone, and irradiation alone groups, respectively.Conclusion:Blockade of NF-B activity induced by radiation with DHMEQ could overcome radio-resistant responses and may become a new therapeutic modality for treating prostate cancer.

Original languageEnglish
Pages (from-to)652-657
Number of pages6
JournalBritish Journal of Cancer
Volume107
Issue number4
DOIs
Publication statusPublished - 2012 Aug 7

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Keywords

  • nuclear factor-κB
  • prostate cancer
  • radiation

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Kozakai, N., Kikuchi, E., Hasegawa, M., Suzuki, E., Ide, H., Miyajima, A., Horiguchi, Y., Nakashima, J., Umezawa, K., Shigematsu, N., & Oya, M. (2012). Enhancement of radiosensitivity by a unique novel NF-B inhibitor, DHMEQ, in prostate cancer. British Journal of Cancer, 107(4), 652-657. https://doi.org/10.1038/bjc.2012.321