2. Academic Validation
  3. Gene Deletion of Microsomal Prostaglandin E Synthase-1 Suppresses Chemically Induced Skin Carcinogenesis

Gene Deletion of Microsomal Prostaglandin E Synthase-1 Suppresses Chemically Induced Skin Carcinogenesis

  • Anticancer Res. 2021 Mar;41(3):1307-1314. doi: 10.21873/anticanres.14888.
Yuka Sasaki 1,  Hiroshi Kuwata 1,  Eri Aida 1,  Tsubasa Ochiai 1,  Daisuke Kamei 1,  Yoshihito Nakatani 1,  Shuntaro Hara 2
Affiliations

Affiliations

  • 1 Division of Health Chemistry, Department of Healthcare and Regulatory Sciences, School of Pharmacy, Showa University, Tokyo, Japan.
  • 2 Division of Health Chemistry, Department of Healthcare and Regulatory Sciences, School of Pharmacy, Showa University, Tokyo, Japan [email protected].
PMID: 33788722 DOI: 10.21873/anticanres.14888
Abstract

Background/aim: Microsomal prostaglandin (PG) E synthase-1 (mPGES-1) is a terminal Enzyme in PGE2 synthesis and highly expressed in several cancers. In this study, to reveal the involvement of mPGES-1 in skin carcinogenesis, the effect of mPGES-1 deficiency on two-stage skin carcinogenesis in mice was investigated.

Materials and methods: A two-stage skin carcinogenesis model using 7,12-dimethylbenz[a]anthracene (DMBA) as an initiator and 12-O-tetradecanoylphorbol-13-acetate (TPA) as a promoter was applied on mPGES-1 knockout (KO) mice and littermate wild-type mice of a Balb/c genetic background.

Results: DMBA/TPA-induced skin carcinogenesis was suppressed in mPGES-1 KO mice. The induction of IL-17 and other inflammatory cytokines by TPA was also suppressed by mPGES-1 deficiency, although DMBA-induced Apoptosis was not affected.

Conclusion: mPGES-1 promotes chemically induced skin carcinogenesis and might play an important role in the TPA-induced promotion phase of the two-stage skin carcinogenesis model. mPGES-1 inhibition may be a therapeutic target for skin Cancer.

Keywords

inflammation; mPGES-1; prostaglandin E2; skin carcinogenesis.

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