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Potentiation of Tumor Necrosis Factor-mediated Apoptosis of Oral Squamous Cell Carcinoma Cells by Adenovirus-mediated Gene Transfer of NF-B Inhibitor

¹ Laboratory of Molecular Signaling and Apoptosis, Department of Biologic and Materials Science,
² Program in Oral Health Science, School of Dentistry, and
³ Program in Cellular and Molecular Biology, University of Michigan, 1011 N. University Ave., Ann Arbor, MI 48109-1078;

*corresponding author, cunywang{at}umich.edu

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

KEY WORDS: NF-kB • gene therapy • tumor necrosis factor • apoptosis • oral squamous cell carcinoma

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