Oral squamous cell carcinoma (SCC) is a malignant tumor which is often resistant to cancer-therapy-mediated apoptosis. The stress-responsive transcription factor nuclear factor kappa B (NF-kappaB), which has been found to be associated with SCC development, plays an essential role in the suppression of tumor necrosis factor (TNF)-mediated apoptosis. Here, we report that an adenovirus-mediated gene transfer of NF-kappaB inhibitor, super-repressor I kappa B alpha (Adv-SR-IkappaBalpha), blocked TNF-induced NF-kappaB activation and sensitized oral SCC cells to TNF killing. Additionally, we found that the inhibition of NFkappaB by Adv-SR-IkappaBalpha enhanced TNF-mediated caspase-8 and -3 activation. These results suggest that NF-kappaB activation is a general mechanism by which oral squamous carcinoma cells are resistant to TNF killing and provide a molecular basis for gene therapy of oral cancer by IkappaBalpha gene transfer in vivo.
Oral squamous cell carcinoma (SCC) is a malignant tumor which is often resistant to cancer-therapy-mediated apoptosis. The stress-responsive transcription factor nuclear factor kappa B (NF-kappaB), which has been found to be associated with SCC development, plays an essential role in the suppression of tumor necrosis factor (TNF)-mediated apoptosis. Here, we report that an adenovirus-mediated gene transfer of NF-kappaB inhibitor, super-repressor I kappa B alpha (Adv-SR-IkappaBalpha), blocked TNF-induced NF-kappaB activation and sensitized oral SCC cells to TNF killing. Additionally, we found that the inhibition of NFkappaB by Adv-SR-IkappaBalpha enhanced TNF-mediated caspase-8 and -3 activation. These results suggest that NF-kappaB activation is a general mechanism by which oral squamous carcinoma cells are resistant to TNF killing and provide a molecular basis for gene therapy of oral cancer by IkappaBalpha gene transfer in vivo.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.