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Endostatin contributes to low-dose paclitaxel-mediated tumor growth and angiogenesis suppression

Research Project

Project/Area Number 18590364
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Experimental pathology
Research InstitutionChiba University

Principal Investigator

HAMANO Yuki  Chiba University, University Hospital, Assistant Professor (90396680)

Co-Investigator(Kenkyū-buntansha) MIKI Yoshio  Tokyo Medical and Dental University, Medical Research Institute, Professor (10281594)
Project Period (FY) 2006 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥3,850,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥450,000)
Fiscal Year 2007: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2006: ¥1,900,000 (Direct Cost: ¥1,900,000)
KeywordsEndostatin / Low-dose chemotherapy / HIF-1α / Paclitaxel / Metastatic tumor / Endogenous angiogenesis inhibitor / Angiogenesis
Research Abstract

Progression of cancer is dependent on angiogenesis. Anti-angiogenic (metronomic or low-dose) chemotherapy is a strategy for optimizing the effects of chemotherapeutics by administrating traditional cytotoxic drugs at lower concentrations without a rest period. We and others have shown that an endogenous angiogenesis inhibitor, thrombospondin-1 (TSP-1), contributes to low-dose cyclophosphamide-mediated endothelial cell apoptosis in the tumor microenvironment. Here, we investigate whether endogenous endostatin serves as an angiogenic inhibitor in low-dose chemotherapy. Low-dose paclitaxel treatment predominantly induced the expression of endostatin in Lewis lung carcinoma cells (LLC), but not in B16F10 melanoma cells (B16F10), endothelial cells or fibroblasts. Low-dose paclitaxel treatment also upregulated the production of endostatin in the circulation of LLC-bearing mice and further reduced the mean tumor volume and blood vessel density. In contrast, sFlt-l, TSP-1 and tumstatin were not affected in the same setting. Lack of endostatin in mice led to the diminished capacity of low-dose paclitaxel to suppress tumor growth. In addition, hypoxia blocked the paclitaxel-mediated upregulation of endostatin while the disruption of HIF-1α significantly increased the expression of endostatin, suggesting that the production of endogenous endostatin is controlled by HIF-1α in the tumor cells. Theses studies demonstrate that endostatin is a key mediator of anti-angiogenic effects observed with low-dose paclitaxel treatment.

Report

(3 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • Research Products

    (3 results)

All 2006 Other

All Presentation (1 results) Remarks (2 results)

  • [Presentation] Endostatin from tumor cells contributes to low-dose paclitaxel-mediated tumor growth suppression via HIF-1α-dependent mechanism2006

    • Author(s)
      Yuki Hamano
    • Organizer
      Frontiers in Cancer Prevention Research Conference
    • Place of Presentation
      Boston, USA
    • Year and Date
      2006-11-13
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Remarks] 「研究成果報告書概要(和文)」より

    • URL

      http://www.geocities.jp/chibanephrology/

    • Related Report
      2007 Final Research Report Summary
  • [Remarks]

    • URL

      http://www.geocities.jp/chibanephrology/

    • Related Report
      2007 Annual Research Report

URL: 

Published: 2006-04-01   Modified: 2016-04-21  

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