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.

Keywords:
Cytosolic phospholipase A2, Cyclooxygenase 2, Oral dysplasia, Squamous cell carcinoma
This content is only available via PDF.
© 2008 S. Karger AG, Basel
2008
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.