Enhanced expression of cyclooxygenase (COX)-2 in human skin epidermal cancer cells: Evidence for growth suppression by inhibiting COX-2 expression

Cyclooxygenase (COX)-2 is one of the rate-limiting enzymes in the conversio n of arachidonic acid to prostaglandins and other eicosanoids. Recent studi es have shown enhanced expression of COX-2 in cancer cells of several tissu es. We investigated the expression of COX-2 and prostaglandin (PG) E-2 prod uction in two human skin epidermal cancer cell lines: cutaneous squamous ce ll carcinoma, HSC-5, and eccrine carcinoma, EcCa. Both COX-2 expression and PGE(2) production were significantly enhanced in cancer cell line; compare d 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 gr owth of untreated cells and cells transfected with COX-2 antisense oligonuc leotide was compared using the MIT assay. Transfection with the antisense o ligonucleotide suppressed COX-2 protein expression and significantly inhibi ted cell growth. The effect of a selective inhibitor of COX-2, NS398, was c ompared with the effect of the antisense oligonucleotide in order to see wh ether COX-2 expression and prostaglandins have selective effects on cell gr owth. COX-2 expression was unchanged by NS398 treatment, whereas NS398 inhi bited cell growth to a certain extent. The degree of growth inhibition was greater with the antisense oligonucleotide than with NS398. Our findings in dicate that COX-2 protein expression is enhanced in skin epidermal cancer c ells and that COX-2 plays a pivotal role in regulating cell growth. Further more, inhibition of COX-2 expression had a more significant effect on growt h suppression than inhibition of COX-2 catalytic activity, suggesting the e xistence of two different signal pathways via COX-2 in regulating cell grow th. (C) 2000 Wiley-Liss, Inc.