title: The effect of indomethacin on paclitaxel sensitivity and apoptosis in oral squamous carcinoma cells: the role of nuclear factor-κB inhibition.
abstract: OBJECTIVE
  To investigate new strategies to intensify chemosensitivity in head and neck squamous cell carcinoma.
  
  
  METHODS
  Oral squamous carcinoma cells were examined for nuclear factor-κB (NF-κB) activation and binding activity by paclitaxel, an agent currently used in head and neck cancer chemotherapy. Electromobility shift assays were used to assess the effect of indomethacin on NF-κB binding activity. Cell proliferation assays were used to study cell sensitivity to paclitaxel. To examine whether cytotoxicity could be increased by specifically inhibiting NF-κB, a dominant negative cell line, inhibitor kappa B-alpha (IκBα), was stably expressed in CA-9-22 cells.
  
  
  RESULTS
  Paclitaxel possessed the capacity to functionally activate NF-κB, as demonstrated by luciferase reporter gene assays and electromobility shift assay. Indomethacin was able to inhibit paclitaxel-mediated NF-κB activation and promote apoptosis of paclitaxel-treated cells at 24 hours. Indomethacin augmented the paclitaxel cell-killing effect. The dominant negative IκBα cell line exhibited increased chemosensitization to paclitaxel by 2- to 10-fold.
  
  
  CONCLUSIONS
  Paclitaxel has the capacity to activate NF-κB in oral squamous carcinoma cells. Indomethacin can reverse this activation to decrease cell proliferation and increase apoptosis. Treatment strategies that combine paclitaxel with indomethacin may have therapeutic benefits attributable to paclitaxel chemosensitization through NF-κB inhibition.
authors.affiliation: Molecular Oncology Program, Department of Otolaryngology, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Emiro E
authors.initials: EE
authors.lastname: Caicedo-Granados
authors.forename: Beverly R
authors.initials: BR
authors.lastname: Wuertz
authors.forename: Paul H
authors.initials: PH
authors.lastname: Marker
authors.forename: Gi Soo
authors.initials: GS
authors.lastname: Lee
authors.forename: Frank G
authors.initials: FG
authors.lastname: Ondrey
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000473:pathology*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D004359:Drug Therapy, Combination; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000473:pathology*; D006801:Humans; D020672:I-kappa B Proteins / Q000032:analysis; D007213:Indomethacin / Q000008:administration & dosage / Q000494:pharmacology*; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D017239:Paclitaxel / Q000008:administration & dosage / Q000494:pharmacology*; D014162:Transfection
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D000072000:NF-KappaB Inhibitor alpha; D017239:Paclitaxel; D007213:Indomethacin