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 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((2)) 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((2)) 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.
Higashi
Y
Y
Department of Dermatology, Kagoshima University Faculty of Medicine, Kagoshima, Japan.
Kanekura
T
T
Kanzaki
T
T
D002384:Catalysis; D002455:Cell Division / Q000187:drug effects / Q000235:genetics; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000096:biosynthesis; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007527:Isoenzymes / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D008565:Membrane Proteins; D020319:Oligodeoxyribonucleotides, Antisense / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D012878:Skin Neoplasms / Q000201:enzymology* / Q000473:pathology; D014162:Transfection; D014407:Tumor Cells, Cultured
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D020319:Oligodeoxyribonucleotides, Antisense; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone