NF-Kappa-B downregulation strategies in head and neck cancer treatment.
OBJECTIVE
Multiple biochemical and genetic strategies were used to downregulate early response gene NF-KappaB, whose activation controls squamous cell cancer-associated pathways.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Patel
Alpen
A
Department of Otolaryngology, University of Minnesota, Minneapolis, Minnesota, USA.
Miller
Lindsay
L
Ahmed
Khalil
K
Ondrey
Frank
F
D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002455:Cell Division; D045744:Cell Line, Tumor; D015536:Down-Regulation; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000096:biosynthesis*
D016328:NF-kappa B