Nf-kappab Inhibition by an Adenovirus Expressed Aptamer Sensitizes Tnfalpha-induced Apoptosis.
From: Department of Surgery, Duke University Medical Center, Box 2633, MSRB Building, Durham, NC 27710, USA.
Biochemical and biophysical research communications
- Publish Date: Aug 2007
- ISSN: 0006-291X
- Volume: 359
- Issue: 3
- Pages: 475-80
- Medium: Print
- Language: English
- Citation (JAMA): Mi Jing, Zhang Xiuwu, Liu Yingmiao, et al. Nf-kappab Inhibition by an Adenovirus Expressed Aptamer Sensitizes Tnfalpha-induced Apoptosis.. Biochem. Biophys. Res. Commun. Aug 2007;359:475-80
Abstract
Prolonged activation of NF-kappaB is involved in the pathogenesis of chronic inflammatory diseases and associated cancers. NF-kappaB activation is considered to be a main mechanism opposing TNFalpha-induced apoptosis. We investigated whether inhibition of NF-kappaB could sensitize tumor and endothelial cells to TNFalpha-induced apoptosis. As such, we developed a novel H1 RNA polymerase III promoter driven adenoviral vector to express an RNA aptamer, Ad-A-p50, which selectively inhibits NF-kappaB activation in the nucleus. This event sensitizes human lung adenocarcinoma cells (A549) and human endothelial cells (HUVEC) to TNFalpha-induced apoptosis through the multiple pathways regulated by NF-kappaB, including Bcl-XL, HIF-1alpha, and VEGF. Our findings also suggest a new mechanism of HIF-1alpha regulation by NF-kappaB in the normoxic environment. RNA aptamer inhibition of NF-kappaB offers exciting opportunities for sensitizing inflammatory and tumor cells to TNFalpha-induced apoptosis.
Mesh Headings (Keywords): Adenoviridae, Apoptosis, Aptamers, Nucleotide, Base Sequence, Cells, Cultured, Down-Regulation, Endothelial Cells, Humans, Molecular Sequence Data, NF-kappa B, Neoplasms, Tumor Necrosis Factor-alpha
Check for Full Text / PubMed Unique Identifier (PMID): 17560552
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