Abstract
NF-κB promotes cell survival against external stress such as radiation. We examined whether NF-κB decoy transfection enhances the antiproliferative effects of radiation on vascular smooth muscle cells (VSMCs) in vitro. The irradiation induced activation or nuclear translocation of NF-κB p65 in VSMCs was confirmed by immunofluorescence. NF-kB decoy transfection resulted in inhibition of the radiation-induced NF-kB activation in VSMCs and the subsequent reduction of transcription and translocation of ICAM, iNOS, and TNF-α, downstream molecules under the control of NF-κB. By using MTT assay, NF-κB decoy augmented the antiproliferative effects of radiation, where the effect of low dose radiation (2 and 8-Gy) of the cells transfected with NF-κB decoy was equivalent to the high dose (16-Gy) irradiated non-transfected cells at 48 h after irradiation: 1.06±0.16, 1.11±0.22, 1.20±0.25, respectively. The decrease in proliferation and survival of the radiation treated cells by flow cytometry analysis showed that NF-κB inhibition did not show any additive effects on the cell cycle of the irradiated VSMCs, while apoptosis was significantly increased after NF-κB decoy transfection in the irradiated VSMCs (apoptosis fraction: 13.33±2.08% vs. 26.29±7.43%, for radiation only vs. radiation+NF-κB decoy transfection, P < 0.05). In addition, at 48 h, NF-κB decoy transfection dose dependently (10 µM vs. 20 µM) inhibited proliferation of 16Gy-irradiated VSMCs, and showed greater antiproliferative efficacy than 100 µM sulfasalazine, a specific NF-κB inhibitor. These results indicate that NF-κB inhibition reduces proliferation and survival of irradiated VSMCs, likely by increased apoptosis rather than additive cell cycle arrest and suggest the possibility of adjunctive gene therapy using NF-κB decoy to improve efficacy and to decrease the adverse effects of intracoronary radiation therapy.
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This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
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Zhang, SY., Park, KW., Oh, S. et al. NF-κB decoy potentiates the effects of radiation on vascular smooth muscle cells by enhancing apoptosis. Exp Mol Med 37, 18–26 (2005). https://doi.org/10.1038/emm.2005.3
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DOI: https://doi.org/10.1038/emm.2005.3
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