Y. Higashi et al., Enhanced expression of cyclooxygenase (COX)-2 in human skin epidermal cancer cells: Evidence for growth suppression by inhibiting COX-2 expression, INT J CANC, 86(5), 2000, pp. 667-671
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.