| Summary: | 碩士 === 長庚大學 === 臨床醫學研究所 === 91 === Recent studies demonstrate that cyclooxygenase-2(COX-2) plays a crucial role in tumorigenesis of human cancers. Hypopharyngeal cancer is one of head and neck cancers with very poor prognosis in Taiwan. Betel nut chewing is the major contributory factor of hypopharyngeal cancer. The aim of this study was investigated the expression of COX-2 in primary tumor tissues of hypopharyngeal cancer and examined the effect of betel nut ingredient on COX-2 expression in normal hypopharyngeal and cancer cells. In addition, we addressed the effect of COX-2-specific inhibitor on hypopharyngeal cancer cells to evaluate whether these inhibitors might be useful for the prevention or treatment of this cancer. Betel nut ingredients promoted COX-2 expression in normal hypophaygeal and hypopharyngeal cancer cells. Our results also showed that COX-2 was overexpressed in hypophaygeal tumor tissues. Transfection of COX-2 expression vector in hypopharyngeal cells or cancer cells stimulated the expression of matrix metalloproteinases and vascular endothelial growth factor. We next tested the effect of COX-2- specific inhibitor NS398 on the proliferation, apoptosis, and cell cycle progression of hypopharyngeal cancer cells. Results showed that specific COX-2 inhibitor (NS398) inhibited growth of cancer cell in a dose-dependent manner and arrested hypopharyngeal cancer cells in G1/S phase. Immunoblotting analysis indicated that expression of G1 cyclins was not change by NS398. Conversely, NS398 obviously increased expression of cyclin-dependent kinases inhibitors p21Waf1 and p27Kip1. Pretreatment of NS398 potently enhanced the cytocidal activity of chemotherapeutic drugs. This effect is possibly mediated via enhancement of apoptosis. Taken together, COX-2 is involved in tumorigenesis of hypophaygeal cancer and COX-2 inhibitors exert anti-proliferative effect on hypopharyngeal cancer cells and may be used in combination with chemotherapeutic drugs for the treatment of hypopharyngeal carcinoma.
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