Expression of Cytosolic Phospholipase A2 and Cyclooxygenase 2 and Their Significance in Human Oral Mucosae, Dysplasias and Squamous Cell Carcinomas

Abstract

Prostaglandin E₂ (PGE₂) plays an important role in promoting carcinogenesis. Cytosolic phospholipase A₂ (cPLA₂) and cyclooxygenase 2 (COX-2) are both key enzymes for PGE₂ biosynthesis. Recent evidence suggests that the coordinated function of cPLA₂ and COX-2 in the arachidonic acid pathway may contribute to the process of carcinogenesis in various tissue types. However, the concomitant effect of these enzymes on oral carcinogenesis remains unclear. In this study,we evaluated the expression of cPLA₂ and COX-2 in normal oral mucosa, dysplastic oral mucosa and squamous carcinoma (SCC) using immunohistochemistry. In an in vitro assay, Tca8113 and KB oral cancer cells were treatedwith NS-398 (a selective inhibitor of COX-2) for varying time intervals: 6, 12, 24, 48 and 72 h. The levels of cPLA₂ and COX-2 expression were evaluated by Western blot, and PGE₂ production was analyzed by radioimmunoassay. We found that cPLA₂ and COX-2 were expressed at higher levels in oral dysplasia and SCC than in normal oral mucosa. cPLA₂ expression was also found to correlate closely with COX-2 expression. Moreover, the enzymatic activities of cPLA₂ and COX-2 were gradually downregulated with longer durations of treatment with NS-398, as demonstrated by a reduction in the amount of PGE₂ production over time. Our data suggest that the coordinated activity of cPLA₂ and COX-2 contribute to the process of oral carcinogenesis, thus identifying cPLA₂ as a potential target for the prevention and treatment of oral cancers.