Background: We investigated whether the endoplasmic reticulum (ER) stress response could be a cyclooxygenase-2 (COX2)-independent mechanism of growth inhibition by celecoxib in a head and neck squamous cell carcinoma (HNSCC) cell line.
Materials and methods: We performed western blotting and reverse transcription polymerase chain reaction to analyze the expression of ER stress response-associated proteins C/EBP homologous protein (CHOP), glucose-regulated protein (GRP)-78 and X-box binding protein-1 (XBP1), after treatment of celecoxib in the SNU-1041 cell line. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was performed to determine the change in growth inhibition by celecoxib after inhibition of the ER stress pathway by CHOP small-interfering RNA (siRNA).
Results: Celecoxib triggered an ER stress response in this HNSCC cell line as shown by activation of CHOP, GRP78 and XBP1. The inhibition of cell proliferation by celecoxib was effectively hindered with CHOP siRNA.
Conclusion: ER stress response could be a COX2-independent anticancer mechanism of celecoxib.
Keywords: COX2; Celecoxib; endoplasmic reticulum stress response; head and neck cancer.