NF-Kappa-B downregulation strategies in head and neck cancer treatment.

Abstract

Multiple biochemical and genetic strategies were used to downregulate early response gene NF-KappaB, whose activation controls squamous cell cancer-associated pathways. NA cells, an oral cavity squamous cell cancer with high NF-KappaB activity, were cultured with biochemical NF-KappaB inhibitors TPCK and Calpain I inhibitor, as well as specific NF-KappaB antisense oligonucleotides. Cell proliferation was measured, as was NF-KappaB downregulation using functional luciferase reporter genes and electromobility shift assays. Significant downregulation of cell proliferation and NF-KappaB functional activity were demonstrated with either biochemical inhibitor, as well as the antisense oligonucleotides; however, additional nonspecific toxicities were observed with control antisense oligonucleotides. NF-KappaB is a potential target for squamous cancer treatment, as it is constitutively upregulated in vitro. Biochemical inhibition of NF-KappaB may be a viable treatment strategy for head and neck squamous cancers.