Blockage of NF-kappaB by IKKbeta- or RelA-siRNA rather than the NF-kappaB super-suppressor IkappaBalpha mutant potentiates adriamycin-induced cytotoxicity in lung cancer cells.

ABSTRACT: Ambiguous roles of genotoxic anticancer therapeutic-induced NF-kappaB activation in regulating gene expression (activation or suppression) and apoptosis (anti- or pro-apoptosis) have recently been suggested. In order to clarify this controversy and determine the usefulness of NF-kappaB blockage for sensitizing anticancer therapy, we have systematically investigated the effect of distinct NF-kappaB-blocking approaches on lung cancer cells' responses to Adriamycin-induced cytotoxicity. The results show that Adriamycin-induced NF-kappaB activation functions as a transcriptional activator triggering the expression of anti-apoptotic genes. Blocking NF-kappaB with IKKbeta- or RelA siRNA substantially sensitized Adriamycin-induced cytotoxicity, suggesting that the NF-kappaB pathway could be a tar

SUBMITTER: Chen W 

PROVIDER: S-EPMC2688738 | biostudies-literature | 2008 Oct

REPOSITORIES: biostudies-literature