NF-kappaB inhibition by an adenovirus expressed aptamer sensitizes TNFalpha-induced apoptosis.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Mi, J; Zhang, X; Liu, Y; Reddy, SK; Rabbani, ZN; Sullenger, BA; Clary, BM

Published Date

  • August 3, 2007

Published In

Volume / Issue

  • 359 / 3

Start / End Page

  • 475 - 480

PubMed ID

  • 17560552

Pubmed Central ID

  • 17560552

International Standard Serial Number (ISSN)

  • 0006-291X

Digital Object Identifier (DOI)

  • 10.1016/j.bbrc.2007.05.125

Language

  • eng

Conference Location

  • United States