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Study on growth suppression and chemoprevention of lung cancer by cyclooxygenase 2 inhibitor

Research Project

Project/Area Number 11670604
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Respiratory organ internal medicine
Research InstitutionAichi Cancer Center Research Institute

Principal Investigator

HIDA Toyoaki  Research Institute, Aichi Cancer Center Research Institute, Researcher, 研究所, 研究員 (80250249)

Co-Investigator(Kenkyū-buntansha) TAKAHASHI Takashi  Molecular Oncology, Aichi Cancer Center Research Institute, Chief, 分子腫瘍学部, 部長 (50231395)
SUGIURA Takahiko  Research Institute, Aichi Cancer Center Research Institute, Researcher, 研究所, 研究員 (50117826)
Project Period (FY) 1999 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2000: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1999: ¥2,500,000 (Direct Cost: ¥2,500,000)
KeywordsLung cancer / prognosis / cyclooxygenase 2 / chemotherapy / radiation / COX-2 inhibitor / apoptosis / combination therapy / cyclooxygenase2 / 予後因子 / 免疫染色 / 抗COX-2抗体
Research Abstract

We recently reported that an increased expression of COX-2 was frequently seen in a specific type of lung cancer, i.e., adenocarcinoma, and was possibly associated with its invasion and metastases. We have also shown the presence of a significant relationship between elevated COX-2 expression and shortened patient survival in a cohort of patients with stage I disease.
We report here that COX-2 inhibitor could inhibit proliferation of non-small cell lung cancer (NSCLC) cell lines in vitro in a dose-dependent manner, in part by inducing apoptosis even at clinically achievable low concentrations. Our observations also suggested that the state of COX-2 expression in NSCLC cells might influence their responsiveness to COX-2 inhibitors. Moreover, we found that COX-2 inhibitor, when used in combination at clinically achievable concentrations, reduced the IC_<50> values of various anticancer agents by up to 77%, although the levels of reduction varied considerably. In radiation sensitivity, COX-2 inhibitor was shown to have an additive effect on the efficacy of irradiation. Since our previous studies have indicated that significantly increased COX-2 expression is present in up to 70% of adenocarcinoma cases, the present findings are of great clinical interest and the recent development of next generation, highly selective COX-2 inhibitors should lead to even greater efficacy for the adjunct use with various anticancer agents in the treatment of high risk patients without compromising their quality of life.

Report

(3 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • Research Products

    (13 results)

All Other

All Publications (13 results)

  • [Publications] Achiwa,H. et al.: "Prognostic significance of elevated cyclooxygenase 2 expression in primary, resected lung adenocarcinomas"Clinical Cancer Research. 5. 1001-1005 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hida,T. et al.: "Cyclooxygenase-2inhibitor induces apoptosis and enhances cytotoxicity of various anticancer agents in non-small cell lung cancer cell lines"Clinical Cancer Research. 6. 2006-2011 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kozaki,K. et al: "Establishment and characterization of a human lung cancer cell line NCl-H460-LNM35 with consistent lymphogenous metastasis via both subcutaneous and orthotopic propagation."Cancer Research. 69. 2535-2540 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Masuda,A. et al: "Protective function of p27KIP1 against apoptosis in small cell lung cancer cells in unfavorable microenvironments."American Journal of pathology. 158. 87-96 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Achiwa, H.et al.: "Prognostic significance of elevated cyclooxygenase2 expression in primary, resected lung adenocarcinomas."Clin. Cancer Res.. 5. 1001-1005 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hida, T.et al.: "Cyclooxygenase-2 inhibitor induces apoptosis and enhances cytotoxicity of various anticancer agents in non-small cell lung cancer cell lines."Clin. Cancer Res.. 6. 2006-2011 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kozaki, K.et al.: "Establishment and characterization of a human lung cancer cell line NCI-H460-LNM35 with consistent lymphogenous metastasis via both subcutaneous and orthotopic"Cancer Res.. 69. 2535-2540 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Masuda, A.et al.: "Protective function of p27^<KIP1> against apoptosis in small cell lung cancer cells in unfavorable microenvironments"Am. J.pathol.. 158. 87-96 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hida,T. et al: "Cyclooxygenase-2inhibitor Induces apoptosis and enhances cytotoxicity of various anticancer agents in non-small cell lung cancer cell lines"Clinical Cancer Research. 6. 2006-2011 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kozaki,K. et al: "Establishment and characte rization of a human lung cancer cell line NCI-H460-LNM35 with consistent lymphogenous metastasis via both subcutaneous and orthotopic propagation"Cancer Research. 69. 2535-2540 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Masuda,A. et al: "Protective function of p27KIP1 against apoptosis in small cell lung cancer cells in unfavorable microenvironments."American Journal of pathology. 158. 87-96 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Achiwa, H. et al: "Prognostic significance of elevated cyclooxygenase 2 expression in primary, resected lung adenocarcinomas"Clinical Cancer Research. 5. 1001-1005 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Hide, T. et al: "Cyclooxygenase-2 inhibitor induces apoptosis and enhances cytotoxicity of various anticancer agents in non-small cell lung cancer cell lines"Clinical Cancer Research. (in press).

    • Related Report
      1999 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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