2000 Fiscal Year Final Research Report Summary
Studies on the roles of the arachidonic acid cascade in the skin cancer development.
| Project/Area Number |
11670840
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Dermatology
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| Research Institution | Kagoshima University |
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Principal Investigator |
KANEKURA Takuro Faculty of Medicine, Kagoshima University, Associate Professor, 医学部, 助教授 (70177509)
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| Project Period (FY) |
1999 – 2000
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| Keywords | skin cancer / cyclooxygenase-2 / retinoic acid / antioxydant / cancer chemoprevention |
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| Research Abstract |
The expression of COX-2 and prostaglandin (PG) E_2 production were investigated 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 to the nontumorigenic 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 by MTT proliferation 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. 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. Based on these findings, we searched for agents which suppress COX-2 expression and examine their effects on cell growth. Since retinoids and antioxidants have been used for chemoprevention of cancers in several tissues, the effects of these agents on COX-2 expression and PGE_2 biosynthesis in skin squamous carcinoma cells were investigated. Treatment with a retinoid [9-cis- retinoic acid (9-cis-RA)] or an antioxidant [pyrrolidinedithiocarbamate (PDTC)] suppressed COX-2 expression and PGE_2 biosynthesis in a concentration-dependent manner. Cell growth was significantly inhibited by 9-cis-RA and PDTC.These results suggest that 9-cis-RA and PDTC may be useful in preventing skin cancer growth and that COX-2 is involved in their protective effects on skin carcinogenesis.
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