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Application of tumor model multicellular spheroids for combination therapy of siRNA targeting HIF-VEGF and radication

Research Project

Project/Area Number 17591285
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Radiation science
Research InstitutionYokohama City University

Principal Investigator

OMURA Motoko  Yokohama City University, School of Medicine, Assistant Professor (70244506)

Co-Investigator(Kenkyū-buntansha) NAKAGAMI Yoshihiro  Yokohama City University, School of Medicine, Visiting Researcher (80347301)
INOUE Tomio  Yokohama City University, Graduate School of Medicine, Visiting Researcher (80134295)
Project Period (FY) 2005 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 2006: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2005: ¥1,200,000 (Direct Cost: ¥1,200,000)
Keywordsspheroid siRNA / HIF / VEGF / radiation / VEGF / 放射線増感剤 / si-RNA / スフェロイド / bcl-2
Research Abstract

Purpose: Expression of hypoxia-inducible factor (HIP) and vascular endothelial growth factor (VEGF) elevated in hypoxic tumor cells that show resistant to radiation. Therefore, we hypothesized inhibiting HIF and VEGF function may enhance the cytotoxic effects of radiation. To clarify this point, we use small interference RNA (siRNA) to inhibit those gene function and multicellular spheroid as a 3D tumor model.
Materials and methods : Monolayer and spheroids of human lung carcinoma cell SQS, were treated with HIF/VEGF siRNA and/or radiation. Quantitative RT-PCR and western blotting were done to analyze gene expression. Cell toxicity was qualified by colony formation assay.
Results : In spheroid, the expression levels of both HIF and VEGF were stably up-regulated compared with monolayer cells. Treatment with HIF or VEGF siRNA displayed inhibition of those mRNA expressions in both monolayer cells and spheroid. Hypoxic condition apparently induced radiation resistance of monolayer cells and spheroid. HIP siRNA but not VEGF siRNA enhanced radiation effect on monolayer cell under hypoxic condition. Either of HIF or VEGF siRNA did not enhance radiation effect on spheroid either normoxic or hypoxic condition.
Conclusion : Spheroids can be applied for evaluating tumor response to down-regulation gene expression by siRNA. HIF siRNA showed radiation enhancement effect on monolayer cells under hypoxic condition in which radiation resistance of cells were induced.

Report

(3 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • Research Products

    (2 results)

All 2006

All Presentation (2 results)

  • [Presentation] siRNA Implicated for Tumor Therapy to Enhance the Radiation Effect on Tumor Cells2006

    • Author(s)
      Yuefen Zou
    • Organizer
      日本放射線腫瘍学会第19回学術大会
    • Place of Presentation
      仙台
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Presentation] Tomio Inoue siRNA Implicated for Tumor Therapy to Enhance the Radiation Effect on Tumor Cells2006

    • Author(s)
      Yuefen Zou, Motoko Omura
    • Organizer
      Japanease Society for Therapeutic Radiation and Oncology, 21st Annual meeting
    • Place of Presentation
      Sendai
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary

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Published: 2005-04-01   Modified: 2016-04-21  

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