Expression of cyclooxygenase (COX)-2 in head and neck cancer and inhibitory effect of COX-2 inhibitors on tumor growth

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This study was designed to examine the immunohistochemical expression of cyclooxygenase (COX)-2 in head and neck cancer, and the inhibitory effect of COX-2 inhibitors on head and neck cancer cell growth. Based on the above experimental data, the chemopreventive potential of COX-2 inhibitors against DMBA-induced hamster cheek pouch carcinogenesis as animal model and synergistic effect of COX-2 inhibitors with anticancer agents as therapeutic strategy are also investigated. The results obtained were as follows.1) The immunohistchemical examination showed the expression of COX-2 protein n both squamous cell carcinoma (SCC) of the head and neck and salivary gland carcinoma (SGC). The expression rate was higher in SGC than SCC. In SCC, COX-2 expression became higher as the degree of tumor differentiation was lower, and undifferentiated carcinomas all showed high expression. In addition, metastatic lesions demonstrated significantly higher expression than primary lesions.2) The COX-2 express … More ion was shown not only in SCC but also in epithelial hyperplasia, epithelial dysplasia and carcinoma in situ. The extent of the expression was increased toward carcinogenesis. There was a close correlation between COX-2 expression and topoisomerase II α expression, and a tendency of poor prognosis in SCC patients with high expression of these enzymes.3) The COX-2 inhibitors inhibited the growth of head and neck cancer cell lines in a dose-dependent manner via apoptosis induction. These effects were more prominent in celecoxib than sulindac and etodolac. Celecoxib inhibited PGE_2 production and COX-2 expression efficiently.4) The non-cytotoxic or less cytotoxic concentrations of celecoxib augmented the growth inhibitory effect of anticancer agents such as adriamycin, vincristine and bleomycin by 2 to 10-fold via increased apoptosis induction.5) Oral administration of celecoxib retarded the onset of carcinoma formation, tumor growth and death in DMBA-induced hamster cheek pouch carcinogenesis model, although all hamsters developed SCC by DMBA application. Less