NF-kappa B decoy potentiates the effects of radiation on vascular smooth muscle cells by enhancing apoptosis
Experimental & Molecular Medicine
;
: 18-26, 2005.
Artículo
en Inglés
| WPRIM
| ID: wpr-18135
ABSTRACT
NF-kappa B promotes cell survival against external stress such as radiation. We examined whether NF-kappa B 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-kappa B 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-alpha, downstream molecules under the control of NF-kappa B. By using MTT assay, NF-kappa B decoy augmented the antiproliferative effects of radiation, where the effect of low dose radiation (2 and 8-Gy) of the cells transfected with NF-kappa B 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-kappa B inhibition did not show any additive effects on the cell cycle of the irradiated VSMCs, while apoptosis was significantly increased after NF-kappa B decoy transfection in the irradiated VSMCs (apoptosis fraction 13.33+/-2.08% vs. 26.29+/-7.43%, for radiation only vs. radiation+NF-kappa B decoy transfection, P < 0.05). In addition, at 48 h, NF-kappa B decoy transfection dose dependently (10 mM vs. 20 mM) inhibited proliferation of 16Gy-irradiated VSMCs, and showed greater antiproliferative efficacy than 100 mM sulfasalazine, a specific NF-kappa B inhibitor. These results indicate that NF-kappa B 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-kappa B decoy to improve efficacy and to decrease the adverse effects of intracoronary radiation therapy.
Texto completo:
Disponible
Índice:
WPRIM (Pacífico Occidental)
Asunto principal:
Aorta
/
Transcripción Genética
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Transfección
/
Ciclo Celular
/
Células Cultivadas
/
FN-kappa B
/
Factor de Necrosis Tumoral alfa
/
Ratas Sprague-Dawley
/
Apoptosis
/
Molécula 1 de Adhesión Intercelular
Límite:
Animales
Idioma:
Inglés
Revista:
Experimental & Molecular Medicine
Año:
2005
Tipo del documento:
Artículo
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