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The enzyme expressions of arachidonic acid cascade in rat colon carcinogenesis and modifying effects of chemopreventive agents

Research Project

Project/Area Number 07670237
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Experimental pathology
Research InstitutionGIFU UNIVERSITY

Principal Investigator

YOSHIMI Naoki  GIFU UNIV., SCHOOL OF MEDICINE,ASSOCIATE PROFESSOR, 医学部, 助教授 (30166996)

Co-Investigator(Kenkyū-buntansha) MORI Hideki  GIFU UNIV., SCHOOL OF MEDICINE,PROFESSOR, 医学部, 教授 (70021433)
田中 卓二  岐阜大学, 医学部, 助教授 (40126743)
Project Period (FY) 1995 – 1997
Project Status Completed (Fiscal Year 1997)
Budget Amount *help
¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1997: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1996: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1995: ¥900,000 (Direct Cost: ¥900,000)
KeywordsARACHIDONIC ACID CASCADE / COLON CARCINOGENESIS / CHEMOPREVENTION / CYCLOOXYGENASE-2 / PHOSPHOLIPASE A2 / RATS / シクロオキシゲナーゼ
Research Abstract

In this study, we examined the mRNA expression of phospholipase A2 and cyclooxygenase (COX)-2 on arachidonic acid cascade in rat colon carcinogenesis. Those expressions in carcinomas were significantly increased, and those in colon mucosa exposed with carcinogen were also induced. In addition, we examined the effects of NS-398, which is a selective COX-2 inhibitor, on the development of aberrant crypt foci (ACF), which is a pre-neoplastic lesion in rat colon carcinogenesis. As the results, NS-398 inhibited the formation of ACF.Now the long-term experiment for the chemoprevention of NS-398 is going on.
[Methods] We used azoxymethane (AOM)-induced colon carcinogenesis model to examine the effect of NS-398,10mg/kg. And the expressions of COX-1 and -2, and cell proiferative potential were examined.
[Results & Discussion] While the number of ACF in rats treated with AOM alone was 0.97(]SY.+-。[)0.32, that is rats treated with AOM and NS-398 (0.42(]SY.+-。[)0.14) was significantly decreased (P<0.001). The expressions of COX-1 and 2 in both groups treated with or without NS-398 were not significantly different. However, the cell proliferative potential in rats treated with NS-398 was decreased compared with that without NS-398. According to the results, COX inhibitors, which are related to the arachidonic acid cascade and non-steroid anti-inflammatory drugs (NAIDs), are considered the chemopreventive agents. Furthermore, as it has been reported that NSAIDs have potentials of apoptosis induction, the apoptotic mechanism of the inhibitory effect of NS-398 in colon carcinogenesis should be examined in future.

Report

(4 results)
  • 1997 Annual Research Report   Final Research Report Summary
  • 1996 Annual Research Report
  • 1995 Annual Research Report
  • Research Products

    (18 results)

All Other

All Publications (18 results)

  • [Publications] Naoki Yoshimi et al.: "The mRNA overexpression of inflammatory euzymes,phospholipase A2 and cyclo-cxygenase,in the large banel macosd and neoplasms of F344 rats treated with…" Cancer Letters. 97. 75-82 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Masumi Suzui et al.: "No involuement of ki-ras or p53 gene mutations in colitis-associated rat colon tumors induced by 1-hydroxyanthraquinone and methylazcxymetanol…" Molecular Carcinogenesis. 12. 193-197 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Naoki Yoshimi et al.: "Telomerase activity of normal tissues and neoplasms in rat colon carcinogenesis induced by methylazoxymethanol acetate and its differnece…" Molecular Carcinogenesis. 16. 1-5 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Yoshinobu Hirose et al.: "Expression of bcl-2,bax,and bcl-xl proteins in azoxymethane-iuduced rat colonic adenocarcinomas" Molecular Carcinogenesis. 19. 25-30 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Naoki Yoshimi et al.: "Ihhibitory effect of NS-398,a selective cyclooxygenase-2 inhibitor,on azoxymethane-induced aberrant cryptfoci in colon…" Japanese J.Cancer Research. 88. 1044-1051 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Masumi Suzui et al.: "No involoement of APC gene mutations in ulcerative colitis-assoctated rat color carcinogenesis induced by 1-hydroxyauthraquinone and…" Molecular Carcinogenesis. 20. 389-393 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Naoki YOSHIMI et al.: "The mRNA overexpression of inflammatory enzymes, phosphlipase A_2 and cyclooxygenase, in the large bowel mucosa and neoplasms of F344 rats treated with naturally occurring carcinogen, 1-hydroxyanthraquinone" Cancer Letters. 97. 75-82 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Masumi SUZUI et al.: "No involvement of Ki-ras and p53 gene mutations in colitis-associated rat colon tumors induced by 1-hydroxyanthraquinone and .methylazoxymethanol acetate" Molecular Carcinogenesis. 12. 193-197 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Naoki YOSHIMI et al.: "Telomerase activity of normal tissues and neoplasms in rat colon carcinogenesis induced by methylazoxymethanol acetate and its difference from that of human colonic tissues" Molecular Carcinogenesis. 16. 1-5 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Yoshinobu HIROSE et al.: "Expression of Bcl-2, Bax and Bcl-X2 proteins in the aozymethane-induced rat colonic adenocarcinomas" Molecular Carcinogenesis. 19. 25-30 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Naoki YOSHIMI et al.: "The inhibitory effects of NS-398, a selective cyclooxygenase-2 inhibitor, on azoxymethane-induced aberrant crypt foci in colon carcinogenesis of F344 rats" Japanese J.Cancer Research. 88. 1044-1051 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Masumi SUZUI et al.: "No involvement of Apc gene mutations in ulcerative colitis-associated rat colon carcinogenesis induced by 1-hydroxyanthraquinone and methylazoxymethanol acetate" Molecular Carcinogenesis. 20. 389-393 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Yoshimi N et al.: "Inhibitory effect of NS-398,a selective cyclocxygenase-2 inhibitor,on azoxymethane induced abemant crypt foci in colon carcinogenesis of F344 rats" Jpn J Cancer Res.88・11. 1044-1051 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Hirose Y, Yoshimi N et al.: "Expression of bcl-2,bax,and bcl-Xl proteins in azoxymethane-induced rat colonic adenocarcinomas" Mol.Carcinogenesis. 19・1. 25-30 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Yoshimi N.et al.: "Telomerase activity or normal tissues and neoplasms in rat colon carcinogenesis induced by methylazoxymetanol acetate and its difference from that of human・・・" Molecular Carcinogenesis. 16・1. 1-5 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Wang A,Yoshimi N.et al.: "Different expression patterns of cyclin A,D1 and E in human eolorectal cancer" J.Cancer Res.Clin.Oncol.122・1. 122-126 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Hirose Y.Yoshimi N et al.: "Early alterations of apoptosis and cell proliferation in azoxymethane induced rat colonic epithelium" Jpn.J.Cancer Res.87・6. 575-582 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Naoki,Yoshimi,et al.: "The mRNA overexpression of inflammatory enzymes, phospholipase A_2 and cyclooxygenase, in the large bowel macosa and necplasms of F344 rats treated with naturally occurning carcinogen," Cancer Letters. 97. 75-82 (1995)

    • Related Report
      1995 Annual Research Report

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Published: 1995-04-01   Modified: 2016-04-21  

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