CANCER CELL BIOLOGY
Enhanced expression of cyclooxygenase (COX)-2 in human skin epidermal cancer cells: Evidence for growth suppression by inhibiting COX-2 expression
Article first published online: 27 APR 2000
Copyright © 2000 Wiley-Liss, Inc.
International Journal of Cancer
Volume 86, Issue 5, pages 667–671, 1 June 2000
How to Cite
Higashi, Y., Kanekura, T. and Kanzaki, T. (2000), Enhanced expression of cyclooxygenase (COX)-2 in human skin epidermal cancer cells: Evidence for growth suppression by inhibiting COX-2 expression. Int. J. Cancer, 86: 667–671. doi: 10.1002/(SICI)1097-0215(20000601)86:5<667::AID-IJC10>3.0.CO;2-Y
- Issue published online: 27 APR 2000
- Article first published online: 27 APR 2000
- Manuscript Revised: 20 DEC 1999
- Manuscript Received: 22 OCT 1999
Cyclooxygenase (COX)-2 is one of the rate-limiting enzymes in the conversion of arachidonic acid to prostaglandins and other eicosanoids. Recent studies have shown enhanced expression of COX-2 in cancer cells of several tissues. We investigated the expression of COX-2 and prostaglandin (PG) E production in two human skin epidermal cancer cell lines: cutaneous squamous cell carcinoma, HSC-5, and eccrine carcinoma, EcCa. Both COX-2 expression and PGE production were significantly enhanced in cancer cell lines compared with the non-tumorigenic human keratinocyte cell line, HaCaT. In order to determine the role of COX-2 in the proliferation of HSC-5 and EcCa, the growth of untreated cells and cells transfected with COX-2 antisense oligonucleotide was compared using the MTT assay. Transfection with the antisense oligonucleotide suppressed COX-2 protein expression and significantly inhibited cell growth. The effect of a selective inhibitor of COX-2, NS398, was compared with the effect of the antisense oligonucleotide in order to see whether COX-2 expression and prostaglandins have selective effects on cell growth. COX-2 expression was unchanged by NS398 treatment, whereas NS398 inhibited cell growth to a certain extent. The degree of growth inhibition was greater with the antisense oligonucleotide than with NS398. Our findings indicate that COX-2 protein expression is enhanced in skin epidermal cancer cells and that COX-2 plays a pivotal role in regulating cell growth. Furthermore, inhibition of COX-2 expression had a more significant effect on growth suppression than inhibition of COX-2 catalytic activity, suggesting the existence of two different signal pathways via COX-2 in regulating cell growth. Int. J. Cancer 86:667–671, 2000. © 2000 Wiley-Liss, Inc.