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-κB), 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-κB inhibitor, super-repressor I kappa B alpha (Adv-SR-IκBα), blocked TNF-induced NF-κB activation and sensitized oral SCC cells to TNF killing. Additionally, we found that the inhibition of NFκB by Adv-SR-IκBα enhanced TNF-mediated caspase-8 and -3 activation. These results suggest that NF-κB 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 IκBα gene transfer in vivo.
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