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Molecular mechanism on the drug resistance and responsiveness against anticancer agents and molecular-target agents

Research Project

Project/Area Number 23300364
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Clinical oncology
Research InstitutionKeio University

Principal Investigator

SUGIMOTO Yoshikazu  慶應義塾大学, 薬学部, 教授 (10179161)

Project Period (FY) 2011-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥21,840,000 (Direct Cost: ¥16,800,000、Indirect Cost: ¥5,040,000)
Fiscal Year 2014: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2013: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2012: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2011: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
KeywordsABCトランスポーター / ABCB1 / ABCG2 / ABCB5 / P-糖タンパク質 / BCRP / 抗がん剤耐性 / SNP / ABC輸送体 / ABC transporter
Outline of Final Research Achievements

The main results of this research project are as follows: (1) The ABCB5 transfectants showed resistance to various anti-cancer agents including docetaxel. Cellular uptake of radiolabeled docetaxel in the transfectants was lower than that in the parental cells, suggesting that ABCB5 mediates the efflux of these anticancer agents. (2) Ubiquitin E3 ligase FBXO15 and ubiquitin-conjugating enzyme UBE2R1 cooperatively ubiquitinated P-glycoprotein and promoted its degradation. (3) Protein phosphatase complex PP5/PPP2R3C negatively regulated the expression and function of P-glycoprotein. (4) A novel acrylonitrile derivative enhanced the antitumor activity of CPT-11 in a xenograft model of BCRP-expressing human colon cancer without a remarkable increase in body weight loss.

Report

(5 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Annual Research Report
  • 2012 Annual Research Report
  • 2011 Annual Research Report
  • Research Products

    (58 results)

All 2015 2014 2013 2012 2011 Other

All Journal Article (14 results) (of which Peer Reviewed: 14 results,  Acknowledgement Compliant: 3 results) Presentation (41 results) Remarks (3 results)

  • [Journal Article] Activity of the dietary flavonoid, apigenin, against multidrug-resistant tumor cells as determined by pharmacogenomics and molecular docking.2015

    • Author(s)
      Mohamed Saeed, Yosikazu Sugimoto, et al.
    • Journal Title

      The Journal of Nutritional Biochemistry

      Volume: VOL. 26 Issue: 1 Pages: 44-56

    • DOI

      10.1016/j.jnutbio.2014.09.008

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Resistance mechanisms of cancer cells to the novel vacuolar H+-ATPase inhibitor archazolid B.2014

    • Author(s)
      Rebecca Hamm, Yoshikazu Sugimoto, et al.
    • Journal Title

      Investigational New Drugs

      Volume: VOL. 32 Issue: 5 Pages: 893-903

    • DOI

      10.1007/s10637-014-0134-1

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Regulations of P-Glycoprotein/ABCB1/MDR1 in Human Cancer Cells.2014

    • Author(s)
      Kazuhiro Katayama, Yoshikazu Sugimoto, et al.
    • Journal Title

      New Journal of Science

      Volume: VOL. 2014 Pages: 476974-476974

    • DOI

      10.1155/2014/476974

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] The lignan, (-)-sesamin reveals cytotoxicity toward cancer cells: pharmacogenomic determination of genes associated with sensitivity or resistance.2014

    • Author(s)
      Mohamed Saeed, Yosikazu Sugimoto, et al.
    • Journal Title

      Phytomedicine

      Volume: VOL. 21 Issue: 5 Pages: 689-696

    • DOI

      10.1016/j.phymed.2014.01.006

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Protein phosphatase complex PP5/PPP2R3C dephosphorylates P-glycoprotein/ABCB1 and down-regulates the expression and function.2014

    • Author(s)
      Kazuhiro Katayama, Yoshikazu Sugimoto, et al.
    • Journal Title

      Cancer Letters

      Volume: VOL. 345 Issue: 1 Pages: 124-131

    • DOI

      10.1016/j.canlet.2013.12.007

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Human ABC transporter ABCG2/BCRP expression in chemoresistance: basic and clinical perspectives for molecular cancer therapeutics.2014

    • Author(s)
      Kohji Noguchi, Yoshikazu Sugimoto, et al.
    • Journal Title

      Pharmacogenomics and Personalized Medicine

      Volume: VOL. 7 Pages: 53-64

    • DOI

      10.2147/pgpm.s38295

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Human Decidua-Derived Mesenchymal Cells Are a Promising Source for the Generation and Cell Banking of Human Induced Pluripotent Stem Cells2013

    • Author(s)
      Tomoko Shofuda, Yoshikazu Sugimoto, et al.
    • Journal Title

      Cell Medicine

      Volume: 4 Issue: 3 Pages: 125-147

    • DOI

      10.3727/215517912x658918

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Biochemical interaction of anti-HCV telaprevir with the ABC transporters P-glycoprotein and breast cancer resistance protein.2013

    • Author(s)
      Yurua F, Yoshikazu Sugimoto, et al.
    • Journal Title

      BMC Research Notes

      Volume: 6 Issue: 1 Pages: 445-445

    • DOI

      10.1186/1756-0500-6-445

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] FBXO15 regulates P-glycoprotein/ABCB1 expression through the ubiquitin-proteasome pathway in cancer cells.2013

    • Author(s)
      Kazuhiro Katayama, Yoshikazu Sugimoto, et al.
    • Journal Title

      Cancer Science

      Volume: 104 Issue: 6 Pages: 694-702

    • DOI

      10.1111/cas.12145

    • Related Report
      2013 Annual Research Report 2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Human decidua-derived mesenchymal cells is a promising source for generation and cell banking of human induced pluripotent stem cells.2013

    • Author(s)
      Tomoko Shofuda
    • Journal Title

      Cell Medicine

      Volume: 印刷中

    • DOI

      10.3727/215517911x658918

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Expression of human ABCB5 confers resistance to taxanes and anthracyclines2012

    • Author(s)
      Takaaki Kawanobe
    • Journal Title

      Biochem Biophys Res Commun

      Volume: VOL.418 Issue: 4 Pages: 736-741

    • DOI

      10.1016/j.bbrc.2012.01.090

    • Related Report
      2012 Annual Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Novel acrylonitrile derivatives, YHO-13177 and YHO-13351, reverse BCRP/ABCG2-mediated drug resistance in vitro and in vivo2011

    • Author(s)
      Ryuta Yamazaki
    • Journal Title

      Mol Cancer Ther

      Volume: VOL.10 Issue: 7 Pages: 1252-1263

    • DOI

      10.1158/1535-7163.mct-10-0874

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A DNA ligand designed to antagonize EBNA1 represses Epstein-Barr virus-induced immortalization2011

    • Author(s)
      Yasuda A., Noguchi K., Minoshima M., Kashiwazaki G., Kanda T., Katayama K., Mitsuhashi J., Bando T., Sugiyama H., Sugimoto Y
    • Journal Title

      Cancer Sci

      Volume: 102(12) Issue: 12 Pages: 2221-2230

    • DOI

      10.1111/j.1349-7006.2011.02098.x

    • NAID

      10030246127

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Novel regulatory role for Kaposi's sarcoma-associated herpesvirus-encode d vFLIP in chemosensitization to bleomycin2011

    • Author(s)
      Yuri Masuda
    • Journal Title

      Biochem Biophys Res Commun

      Volume: VOL.415 Issue: 2 Pages: 305-312

    • DOI

      10.1016/j.bbrc.2011.10.050

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Presentation] Aurora kinase阻害薬耐性細胞の解析2015

    • Author(s)
      本釜圭太
    • Organizer
      日本薬学会第135年会
    • Place of Presentation
      デザイン・クリエイティブセンター神戸(神戸市)
    • Year and Date
      2015-03-28
    • Related Report
      2014 Annual Research Report
  • [Presentation] MAPK系によるP=糖タンパク質/ABCB1の分解制御2015

    • Author(s)
      片山和浩
    • Organizer
      日本薬学会第135年会
    • Place of Presentation
      兵庫医療大学(神戸市)
    • Year and Date
      2015-03-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] FLT3/Pim-1系路によるP-gpの発現調節2015

    • Author(s)
      高見麻由
    • Organizer
      日本薬学会第135年会
    • Place of Presentation
      兵庫医療大学(神戸市)
    • Year and Date
      2015-03-26
    • Related Report
      2014 Annual Research Report
  • [Presentation] EMTに伴って誘導されたSP細胞の性質の検討2015

    • Author(s)
      加藤優
    • Organizer
      日本薬学会第135年会
    • Place of Presentation
      兵庫医療大学(神戸市)
    • Year and Date
      2015-03-26
    • Related Report
      2014 Annual Research Report
  • [Presentation] Polo-like kinase阻害剤耐性因子の探索2014

    • Author(s)
      野々宮悠真
    • Organizer
      第58回日本薬学会関東支部大会
    • Place of Presentation
      昭和薬科大学(町田市)
    • Year and Date
      2014-10-04
    • Related Report
      2014 Annual Research Report
  • [Presentation] caspase-8のsiRNAの導入がPolo like kinase 阻害剤の効果に与える影響2014

    • Author(s)
      笠垣貴大
    • Organizer
      第58回日本薬学会関東支部大会
    • Place of Presentation
      昭和薬科大学(町田市)
    • Year and Date
      2014-10-04
    • Related Report
      2014 Annual Research Report
  • [Presentation] ヒト結腸がん細胞の上皮間葉転換による抗がん剤感受性の変動2014

    • Author(s)
      加藤優
    • Organizer
      第58回日本薬学会関東支部大会
    • Place of Presentation
      昭和薬科大学(町田市)
    • Year and Date
      2014-10-04
    • Related Report
      2014 Annual Research Report
  • [Presentation] Aurora kinase 阻害剤効果予測因子の探索2014

    • Author(s)
      本釜圭太
    • Organizer
      第58回日本薬学会関東支部大会
    • Place of Presentation
      昭和薬科大学(町田市)
    • Year and Date
      2014-10-04
    • Related Report
      2014 Annual Research Report
  • [Presentation] PLK阻害剤耐性細胞の樹立と耐性形質の解析2014

    • Author(s)
      野口耕司
    • Organizer
      第73回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜(横浜市)
    • Year and Date
      2014-09-25
    • Related Report
      2014 Annual Research Report
  • [Presentation] プロテアソーム阻害剤はMEK阻害によるP-glycoprotein/ABCB1の発現低下を抑制する2014

    • Author(s)
      片山和浩
    • Organizer
      第73回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜(横浜市)
    • Year and Date
      2014-09-25
    • Related Report
      2014 Annual Research Report
  • [Presentation] Polo-like kinase阻害剤に対する薬剤感受性規定因子の探索2014

    • Author(s)
      野口耕司
    • Organizer
      第18回日本がん分子標的治療学会
    • Place of Presentation
      仙台市情報・産業プラザ(仙台市)
    • Year and Date
      2014-09-16
    • Related Report
      2014 Annual Research Report
  • [Presentation] MEK阻害剤によるP-糖タンパク質/ABCB1の発現低下におけるプロテアソーム分解の関与2014

    • Author(s)
      片山和浩
    • Organizer
      第18回日本がん分子標的治療学会
    • Place of Presentation
      仙台市情報・産業プラザ(仙台市)
    • Year and Date
      2014-09-16
    • Related Report
      2014 Annual Research Report
  • [Presentation] P-糖タンパク質/ABCB1のリン酸化と機能制御2014

    • Author(s)
      片山和浩
    • Organizer
      日本薬学会第134年会
    • Place of Presentation
      熊本大学(熊本)
    • Related Report
      2013 Annual Research Report
  • [Presentation] KSHV由来RTAによるヒトIL-10プロモーターの活性制御機構2014

    • Author(s)
      野口耕司
    • Organizer
      日本薬学会第134年会
    • Place of Presentation
      熊本大学(熊本)
    • Related Report
      2013 Annual Research Report
  • [Presentation] PP5/PPP2R3CによるP-糖タンパク質/ABCB1の発現制御2013

    • Author(s)
      片山和浩
    • Organizer
      第17回日本がん分子標的治療学会学術総会
    • Place of Presentation
      国立京都国際会館(京都)
    • Related Report
      2013 Annual Research Report
  • [Presentation] がんウイルスKSHV由来の転写調節因子RTA/ORF50に対するHDAC阻害剤とBromodomain阻害剤の効果2013

    • Author(s)
      野口耕司
    • Organizer
      第17回日本がん分子標的治療学会学術総会
    • Place of Presentation
      国立京都国際会館(京都)
    • Related Report
      2013 Annual Research Report
  • [Presentation] ABCB5遺伝子導入細胞の薬剤耐性2013

    • Author(s)
      近藤慎吾
    • Organizer
      第72回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜(横浜)
    • Related Report
      2013 Annual Research Report
  • [Presentation] PP5/PPP2R3C複合体はP-糖タンパク質/ABCB1発現を抑制する2013

    • Author(s)
      片山和浩
    • Organizer
      第72回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜(横浜)
    • Related Report
      2013 Annual Research Report
  • [Presentation] c-Myc and HDAC3 suppress KSHV Replication and Transcription Activator (RTA) protein2013

    • Author(s)
      野口耕司
    • Organizer
      第72回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜(横浜)
    • Related Report
      2013 Annual Research Report
  • [Presentation] Plk1阻害剤によるアポトーシス誘導機構の解析2013

    • Author(s)
      田中伯享
    • Organizer
      第57回日本薬学会関東支部大会
    • Place of Presentation
      帝京大学(東京)
    • Related Report
      2013 Annual Research Report
  • [Presentation] ヒトABCB5のメタボローム解析2012

    • Author(s)
      近藤慎吾
    • Organizer
      日本薬学会第132年会
    • Place of Presentation
      北海道大学(北海道)
    • Year and Date
      2012-03-31
    • Related Report
      2011 Annual Research Report
  • [Presentation] ABCB5発現細胞におけるBSOの影響2012

    • Author(s)
      川野邊峻哲
    • Organizer
      日本薬学会第132年会
    • Place of Presentation
      北海道大学(北海道)
    • Year and Date
      2012-03-31
    • Related Report
      2011 Annual Research Report
  • [Presentation] がん関連ウィルスKSHC由来の転写因子RTAの機能制御に関する解析2012

    • Author(s)
      野口耕司
    • Organizer
      日本薬学会第132年会
    • Place of Presentation
      北海道大学(北海道)
    • Year and Date
      2012-03-30
    • Related Report
      2011 Annual Research Report
  • [Presentation] 抗がん剤排出トランスポーターのSNP2012

    • Author(s)
      杉本芳一
    • Organizer
      第45回制癌剤適応研究会
    • Place of Presentation
      国際ファッションセンター(東京都)(招待講演)
    • Year and Date
      2012-03-02
    • Related Report
      2011 Annual Research Report
  • [Presentation] Functional analysis of human ABCB52011

    • Author(s)
      Yoshikazu Sugimoto
    • Organizer
      The JSPS/iCeMS Joint International Symposium ABC 2011 in Kyoto
    • Place of Presentation
      京都大学(京都府)(招待講演)
    • Year and Date
      2011-11-17
    • Related Report
      2011 Annual Research Report
  • [Presentation] ヒトABCB5はATPase活性を有するが、ABCB1の基質は活性に影響を与えない2011

    • Author(s)
      川野邊峻哲
    • Organizer
      第55回日本薬学会関東支部大会
    • Place of Presentation
      東邦大学薬学部(千葉県)
    • Year and Date
      2011-10-08
    • Related Report
      2011 Annual Research Report
  • [Presentation] KSHV由来のRTA/ORF50の転写活性を変動させる薬物の探索2011

    • Author(s)
      原一郎
    • Organizer
      第55回日本薬学会関東支部大会
    • Place of Presentation
      東邦大学薬学部(千葉県)
    • Year and Date
      2011-10-08
    • Related Report
      2011 Annual Research Report
  • [Presentation] P-糖タンパク質/ABCB1結合タンパク質の同定2011

    • Author(s)
      片山和浩
    • Organizer
      第70回日本癌学会学術総会
    • Place of Presentation
      名古屋国際会議場(愛知県)
    • Year and Date
      2011-10-05
    • Related Report
      2011 Annual Research Report
  • [Presentation] ヒトABCB5のATPase活性の検討2011

    • Author(s)
      川野邊峻哲
    • Organizer
      第70回日本癌学会学術総会
    • Place of Presentation
      名古屋国際会議場(愛知県)
    • Year and Date
      2011-10-04
    • Related Report
      2011 Annual Research Report
  • [Presentation] ウイルス由来vFLIPによるブレオマイシン誘導G2/M期チェックポイントの制御2011

    • Author(s)
      野口耕司
    • Organizer
      第70回日本癌学会学術総会
    • Place of Presentation
      名古屋国際会議場(愛知県)
    • Year and Date
      2011-10-03
    • Related Report
      2011 Annual Research Report
  • [Presentation] EBV-induced immortalization is inhibited by polyamide targeting EBNA1-oriP binding2011

    • Author(s)
      Kohji Noguchi
    • Organizer
      XV International Congress of Virology/IUMS2011 Congress
    • Place of Presentation
      札幌コンベンションセンター(北海道)
    • Year and Date
      2011-09-13
    • Related Report
      2011 Annual Research Report
  • [Presentation] EBNA1-OriP結合を阻害するポリアミド化合物によるEBウイルス感染細胞の不死化阻害2011

    • Author(s)
      野口耕司
    • Organizer
      第15回日本がん分子標的治療学会
    • Place of Presentation
      ホテル日航東京(東京都)
    • Year and Date
      2011-06-23
    • Related Report
      2011 Annual Research Report
  • [Presentation] FBXO15 is an F-box protein in E3 ligase complex for P-glycoprotein.

    • Author(s)
      Kazuhiro Katayama
    • Organizer
      AACR Annual Meeting 2012
    • Place of Presentation
      McCormick Place (Chicago, IL, USA)
    • Related Report
      2012 Annual Research Report
  • [Presentation] P-糖タンパク質に対するユビキチンE3リガーゼFBX015の同定と機能解析

    • Author(s)
      片山和浩
    • Organizer
      第16回日本がん分子標的治療学会
    • Place of Presentation
      西日本総合展示場(北九州)
    • Related Report
      2012 Annual Research Report
  • [Presentation] KSHV関連リンパ腫に対するHDAC阻害薬と抗ウイルス薬の相乗効果の分子基盤

    • Author(s)
      野口耕司
    • Organizer
      第16回日本がん分子標的治療学会
    • Place of Presentation
      西日本総合展示場(北九州)
    • Related Report
      2012 Annual Research Report
  • [Presentation] FBXO15によるP-糖タンパク質/ABCB1の分解制御

    • Author(s)
      片山和浩
    • Organizer
      第71回日本癌学会学術総会
    • Place of Presentation
      ロイトン札幌(札幌)
    • Related Report
      2012 Annual Research Report
  • [Presentation] Plk阻害による抗有糸分裂効果はカスパーゼの活性化に依存する

    • Author(s)
      田中伯享
    • Organizer
      第71回日本癌学会学術総会
    • Place of Presentation
      ロイトン札幌(札幌)
    • Related Report
      2012 Annual Research Report
  • [Presentation] 新規Pim kinase阻害薬の抗腫瘍効果

    • Author(s)
      近藤慎吾
    • Organizer
      第71回日本癌学会学術総会
    • Place of Presentation
      ロイトン札幌(札幌)
    • Related Report
      2012 Annual Research Report
  • [Presentation] ヒト大腸がん細胞のSnail誘導上皮間葉転換におけるABC輸送体の発現

    • Author(s)
      石川宣明
    • Organizer
      第71回日本癌学会学術総会
    • Place of Presentation
      ロイトン札幌(札幌)
    • Related Report
      2012 Annual Research Report
  • [Presentation] KSHV由来のRTA/ORF50の機能制御に関するリシン残基の関与

    • Author(s)
      野口耕司
    • Organizer
      日本薬学会第133年会
    • Place of Presentation
      パシフィコ横浜(横浜)
    • Related Report
      2012 Annual Research Report
  • [Presentation] PP5/PPP2R3CによるP-糖タンパク質/ABCB1の発現と活性制御

    • Author(s)
      片山和浩
    • Organizer
      日本薬学会第133年会
    • Place of Presentation
      パシフィコ横浜(横浜)
    • Related Report
      2012 Annual Research Report
  • [Remarks] 化学療法学講座

    • URL

      http://www.pha.keio.ac.jp/research/ct/chair.html

    • Related Report
      2014 Annual Research Report
  • [Remarks] 化学療法学講座

    • URL

      http://www.pha.keio.ac.jp/laboratory/laboratory15

    • Related Report
      2013 Annual Research Report
  • [Remarks] 化学療法学

    • URL

      http://www.pha.keio.ac.jp/laboratory/laboratory15

    • Related Report
      2012 Annual Research Report

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Published: 2011-04-06   Modified: 2019-07-29  

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