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Escin inhibits angiogenesis by blocking nuclear factor-kB activation in pancreatic cancer cell lines

Research Project

Project/Area Number 19K18157
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 55020:Digestive surgery-related
Research InstitutionNagoya City University

Principal Investigator

Omi Kan  名古屋市立大学, 医薬学総合研究院(医学), 研究員 (60825488)

Project Period (FY) 2019-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Keywords膵癌 / 血管新生 / NF-kB / VEGF / IL-8 / anigiogenesis / 抗腫瘍効果 / エスシン / NF-κB
Outline of Research at the Start

膵癌は消化器癌のなかでも悪性度の最も高い癌である.根治手術を行っても5年生存率は20%に満たず,抗癌剤や放射線治療の効果も十分ではない.膵癌に抗癌剤が効きにくい理由として,癌細胞内の NF-κBの活性が高く,血管新生能が高いことが言われている.NF-κBの抑制により,腫瘍の血管新生因子のVEGFやIL-8の産生は低下し,腫瘍増殖にかかわる血管新生は抑制される.NF-κBは新規分子標的薬剤のターゲットになりうると考えられる.低用量でNF-κBの活性を抑える新規薬剤の開発を求めて西洋トチノキ由来の天然化合物エスシンに着目した.各種実験にてその抗腫瘍効果を確認していく.

Outline of Final Research Achievements

Escin, from the horse chestnut, has been reported to suppress the NF-κB in several cancers. Our previous study showed that NF-κB enhanced angiogenesis in PaCa. We examined whether escin inhibited angiogenesis by blocking NF-κB activation in PaCa. Escin, in concentration of over 10 μM, inhibited the proliferation of several PaCa cell lines. In immunocytochemical staining, escin inhibited the nuclear translocation of NF-κB. NF-κB ELISA showed that NF-κB activity in escin-treated PaCa cells was inhibited and RT-PCR showed that the mRNA expression levels of IL-8 and VEGF were suppressed following escin treatment in the PaCa cell lines. ELISA showed escin decreased the production of IL-8 and VEGF. Tube formation in immortalized human endothelial cells was inhibited following incubation with the supernatants from escin-treated PaCa cells. These results indicated that escin inhibited angiogenesis by reducing the production of IL-8 and VEGF via blocking NF-κB activity in PaCa.

Academic Significance and Societal Importance of the Research Achievements

膵癌は悪性度が極めて高く、より効果のある新規治療薬の開発は急務である。我々は今までに、膵癌の転移や血管新生に転写因子NF-κBが重要な役割を果たしていることを報告してきた。転移能の高い膵癌は恒常的にNF-κB の活性が高く、その下流のVEGFやIL-8といった血管新生因子の産生能を亢進し悪性度を高めている。以上より、NF-κBは新規分子標的薬のターゲットになりうるが、既存のNF-κB阻害薬は副作用が強く長期投与が困難で、膵癌では臨床応用に至っていない。今回、天然化合物エスシンが膵癌の血管新生能を低下させることが示唆されたため、動物実験等を今後行い、臨床応用につなげられる可能性がある。

Report

(5 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (3 results)

All 2021 2020 2019

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (2 results)

  • [Journal Article] Escin inhibits angiogenesis by suppressing interleukin?8 and vascular endothelial growth factor production by blocking nuclear factor?κB activation in pancreatic cancer cell lines2021

    • Author(s)
      Omi Kan、Matsuo Yoichi、Ueda Goro、Aoyama Yoshinaga、Kato Tomokatsu、Hayashi Yuichi、Imafuji Hiroyuki、Saito Kenta、Tsuboi Ken、Morimoto Mamoru、Ogawa Ryo、Takahashi Hiroki、Takiguchi Shuji
    • Journal Title

      Oncology Reports

      Volume: 45 Issue: 5 Pages: 1-9

    • DOI

      10.3892/or.2021.8006

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 膵癌に対するエスシンの抗腫瘍効果の検討2020

    • Author(s)
      大見 関、松尾洋一、ほか
    • Organizer
      第120回日本外科学会定期学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] Escinの膵癌細胞株に対する抗腫瘍効果の検討2019

    • Author(s)
      大見 関、松尾洋一、ほか
    • Organizer
      第57回日本癌治療学会学術集会
    • Related Report
      2019 Research-status Report

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Published: 2019-04-18   Modified: 2024-01-30  

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