The effect of indomethacin on paclitaxel sensitivity and apoptosis in oral squamous carcinoma cells: The role of nuclear factor-κb inhibition

Emiro E. Caicedo-Granados, Beverly R. Wuertz, Paul H. Marker, Gi Soo Lee, Frank G. Ondrey

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

Objective: To investigate new strategies to intensify chemosensitivity in head and neck squamous cell carcinoma. Design: 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 cellkilling 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.

Original languageEnglish (US)
Pages (from-to)799-805
Number of pages7
JournalArchives of Otolaryngology - Head and Neck Surgery
Volume137
Issue number8
DOIs
StatePublished - Aug 2011

Fingerprint Dive into the research topics of 'The effect of indomethacin on paclitaxel sensitivity and apoptosis in oral squamous carcinoma cells: The role of nuclear factor-κb inhibition'. Together they form a unique fingerprint.

  • Cite this