Abstract
Pain is the most disruptive influence on the quality of prognosis among head and neck squamous cell carcinoma (HNSCC) patients. The development of pain is closely associated with tumor growth and inflammation in the cancer patients. Notably, cyclooxygenase-2 (COX-2) is an important mediator during inflammation. Celecoxib, a selective inhibitor of COX-2, was hailed as a promising chemopreventive agent for HNSCC. Dose-dependent cardiac toxicity limits long-term use of celecoxib. However, the toxicity can be diminished by lowering the dosage. In this study, we hypothesized that a combinatory strategy to reduce cancer pain via two distinct pathways, tumor grown inhibition and inflammation blockade, which would enhance analgesia effect induced by HNSCC. We found that treatment of cetuximab (C225), a monoclonal anti-epidermal growth factor receptor (EGFR) antibody, with low-dose celecoxib results in a more pronounced anticancer effect in HNSCC than either agent alone. More noticeably, the combination could downregulate the phosphorylation of constitutively active extracellular signal regulated kinase (ERK) in CAL-27 and Fadu cells. Furthermore, combination therapy enhancing S phase arrest and downregulating cyclin D1 was observed in ...Continue Reading
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