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Basic studies on P2Y12 receptor antagonists as candidates for antimetastatic agents

Research Project

Project/Area Number 26460244
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Medical pharmacy
Research InstitutionMukogawa Women's University

Principal Investigator

Nakamura Kazuki  武庫川女子大学, 薬学部, 教授 (20299093)

Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2015: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
KeywordsP2Y12受容体拮抗薬 / クロピドグレル / チクロピジン / がん転移 / がん細胞浸潤能 / がん細胞遊走能 / Vimentin / MMP-2 / 血小板 / マウスメラノーマ細胞 / Clopidogrel / 遊走能 / 血行性肺転移モデル / 抗凝固作用
Outline of Final Research Achievements

First, we demonstrated that orally administered Clopidogrel, a P2Y12 receptor antagonist, inhibited lung metastasis in mice intravenously injected with B16-BL6 mouse melanoma cells.
To elucidate the mechanism of antimetastatic action of P2Y12 receptor antagonists, the effects of Clopidogrel and Ticlopidine on cell motility and invasiveness were measured by chemotaxis assay and chemoinvasion assay, respectively. Clopidogrel significantly reduced both cell motility and invasiveness in a dose-dependent manner. Ticlopidine also significantly reduced cell motility in a dose-dependent manner. Furthermore, Clopidogrel reduced the protein expression level of Vimentin, while Ticlopidine significantly reduced Matrix metalloproteinase-9 (MMP-9) activity and the protein expression level of MMP-2.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (10 results)

All 2017 2016 2015 Other

All Journal Article (5 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 5 results,  Open Access: 3 results,  Acknowledgement Compliant: 1 results) Presentation (3 results) Remarks (2 results)

  • [Journal Article] Middle molecular weight heparinyl amino acid derivatives (MHADs) function as indirect radical scavengers in vitro2016

    • Author(s)
      Seiichi Takeda, Takao Toda and Kazuki Nakamura
    • Journal Title

      Pharmacology and Pharmacy

      Volume: 7 Pages: 117-123

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Inhibitory effects of medium molecular weight heparinyl amino acid derivatives on ischemic paw edema in mice2016

    • Author(s)
      Seiichi Takeda, Takao Toda and Kazuki Nakamura
    • Journal Title

      In Vivo

      Volume: 30 Pages: 433-437

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effects of medium molecular weight heparinyl phenylalanine on superoxide dismutase activity in mice2016

    • Author(s)
      Seiichi Takeda, Takao Toda and Kazuki Nakamura
    • Journal Title

      In Vivo

      Volume: 30 Pages: 841-844

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Antitumor activity of melinjo (Gnetum gnemon L.) seed extract in human and murine tumor models in vitro and in a colon-26 tumor-bearing mouse model in vivo2015

    • Author(s)
      Narayanan K. Narayanan, Kazuhiro Kunimasa, Yukio Yamori, Mari Mori, Hideki Mori, Kazuki Nakamura, George Miller, Upender Manne, Amit K. Tiwari and Bhagavathi Narayanan
    • Journal Title

      Cancer Medicine

      Volume: 4 Issue: 11 Pages: 1767-1780

    • DOI

      10.1002/cam4.520

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Anticancer and antimetastatic effects of cordycepin, an active component of Cordyceps sinensis2015

    • Author(s)
      Kazuki Nakamura, Kazumasa Shinozuka, Noriko Yoshikawa
    • Journal Title

      Journal of Pharmacological Sciences

      Volume: 127 Issue: 1 Pages: 53-56

    • DOI

      10.1016/j.jphs.2014.09.001

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] 血小板凝集抑制薬クロピドグレルのがん転移抑制作用機序の追究2017

    • Author(s)
      渡部彩葉、吉川紀子、木下恵理子、畑井麻友子、籠田智美、篠塚和正、中村一基
    • Organizer
      日本薬学会第137年会
    • Place of Presentation
      仙台国際センター
    • Year and Date
      2017-03-27
    • Related Report
      2016 Annual Research Report
  • [Presentation] 血小板凝集抑制薬クロピドグレルのがん転移抑制薬としての可能性について2016

    • Author(s)
      向井裕香、山本理紗子、冨田安子、吉川紀子、畑井麻友子、田中マチ子、籠田智美、篠塚和正、中村一基
    • Organizer
      日本薬学会第 136 年会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2016-03-27
    • Related Report
      2015 Research-status Report
  • [Presentation] マウスメラノーマ細胞の転移能とがん抑制遺伝子Pdcd4発現量の関係2016

    • Author(s)
      栗林千尋、北佐知子、吉川紀子、大石真子、櫻井文香、畑井麻友子、田中マチ子、籠田智美、篠塚和正、中村一基
    • Organizer
      日本薬学会第 136 年会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2016-03-27
    • Related Report
      2015 Research-status Report
  • [Remarks] 武庫川女子大学薬学部薬理学I研究室

    • URL

      http://ph.mukogawa-u.ac.jp/~yakuri1/

    • Related Report
      2016 Annual Research Report 2014 Research-status Report
  • [Remarks] 武庫川女子大学薬学部薬理学Ⅰ研究室

    • URL

      http://ph.mukogawa-u.ac.jp/~yakuri1/

    • Related Report
      2015 Research-status Report

URL: 

Published: 2014-04-04   Modified: 2018-03-22  

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