Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2005-3-11
pubmed:abstractText
NF-kappaB promotes cell survival against external stress such as radiation. We examined whether NF-kappaB 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-kappaB p65 in VSMCs was confirmed by immunofluorescence. NF-kappaB decoy transfection resulted in inhibition of the radiation-induced NF-kappaB activation in VSMCs and the subsequent reduction of transcription and translocation of ICAM, iNOS, and TNF-alpha, downstream molecules under the control of NF-kappaB. By using MTT assay, NF-kappaB decoy augmented the antiproliferative effects of radiation, where the effect of low dose radiation (2 and 8-Gy) of the cells transfected with NF-kappaB 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-kappaB inhibition did not show any additive effects on the cell cycle of the irradiated VSMCs, while apoptosis was significantly increased after NF-kappaB decoy transfection in the irradiated VSMCs (apoptosis fraction: 13.33+/-2.08% vs. 26.29+/-7.43%, for radiation only vs. radiation+NF-kappaB decoy transfection, P < 0.05). In addition, at 48 h, NF-kappaB decoy transfection dose dependently (10 microM vs. 20 microM) inhibited proliferation of 16Gy-irradiated VSMCs, and showed greater antiproliferative efficacy than 100 microM sulfasalazine, a specific NF-kappaB inhibitor. These results indicate that NF-kappaB 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-kappaB decoy to improve efficacy and to decrease the adverse effects of intracoronary radiation therapy.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1226-3613
pubmed:author
pubmed:issnType
Print
pubmed:day
28
pubmed:volume
37
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
18-26
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:15761248-Animals, pubmed-meshheading:15761248-Aorta, pubmed-meshheading:15761248-Apoptosis, pubmed-meshheading:15761248-Cell Cycle, pubmed-meshheading:15761248-Cell Proliferation, pubmed-meshheading:15761248-Cells, Cultured, pubmed-meshheading:15761248-Gamma Rays, pubmed-meshheading:15761248-Intercellular Adhesion Molecule-1, pubmed-meshheading:15761248-Male, pubmed-meshheading:15761248-Muscle, Smooth, Vascular, pubmed-meshheading:15761248-Myocytes, Smooth Muscle, pubmed-meshheading:15761248-NF-kappa B, pubmed-meshheading:15761248-Nitric Oxide Synthase, pubmed-meshheading:15761248-Nitric Oxide Synthase Type II, pubmed-meshheading:15761248-Protein Transport, pubmed-meshheading:15761248-Rats, pubmed-meshheading:15761248-Rats, Sprague-Dawley, pubmed-meshheading:15761248-Transcription, Genetic, pubmed-meshheading:15761248-Transfection, pubmed-meshheading:15761248-Tumor Necrosis Factor-alpha
pubmed:year
2005
pubmed:articleTitle
NF-kappaB decoy potentiates the effects of radiation on vascular smooth muscle cells by enhancing apoptosis.
pubmed:affiliation
Cardiovascular Laboratory, Clinical Research Institute, Seoul National University Hospital, Seoul 110-744, Korea.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't