TY - JOUR
T1 - Enhancement of radiosensitivity by a unique novel NF-B inhibitor, DHMEQ, in prostate cancer
AU - Kozakai, N.
AU - Kikuchi, E.
AU - Hasegawa, M.
AU - Suzuki, E.
AU - Ide, H.
AU - Miyajima, A.
AU - Horiguchi, Y.
AU - Nakashima, J.
AU - Umezawa, K.
AU - Shigematsu, N.
AU - Oya, M.
PY - 2012/8/7
Y1 - 2012/8/7
N2 - 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.
AB - 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.
KW - nuclear factor-κB
KW - prostate cancer
KW - radiation
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UR - http://www.scopus.com/inward/citedby.url?scp=84864882225&partnerID=8YFLogxK
U2 - 10.1038/bjc.2012.321
DO - 10.1038/bjc.2012.321
M3 - Article
C2 - 22805327
AN - SCOPUS:84864882225
SN - 0007-0920
VL - 107
SP - 652
EP - 657
JO - British Journal of Cancer
JF - British Journal of Cancer
IS - 4
ER -
