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Enhanced expression of cyclooxygenase (COX)‐2 in human skin epidermal cancer cells: Evidence for growth suppression by inhibiting COX‐2 expression
Author(s) -
Higashi Yuko,
Kanekura Takuro,
Kanzaki Tamotsu
Publication year - 2000
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(20000601)86:5<667::aid-ijc10>3.0.co;2-y
Subject(s) - transfection , hacat , cell growth , cell culture , biology , cyclooxygenase , cancer cell , microbiology and biotechnology , growth inhibition , cancer research , cell , cancer , enzyme , biochemistry , genetics
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 2production in two human skin epidermal cancer cell lines: cutaneous squamous cell carcinoma, HSC‐5, and eccrine carcinoma, EcCa. Both COX‐2 expression and PGE 2production 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.