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Journal of Dental Research
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Biological

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

S. Chen1, A. Fribley1,2 and C.-Y. Wang1,*,2,3

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;

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

Key Words: NF-kB • gene therapy • tumor necrosis factor • apoptosis • oral squamous cell carcinoma

Journal of Dental Research, Vol. 81, No. 2, 98-102 (2002)
DOI: 10.1177/154405910208100203
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