• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Organ-specific inactivation of cancer multidrug resistance by regulating membrane scaffold proteins

Research Project

Project/Area Number 15K08078
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Medical pharmacy
Research InstitutionTakasaki University of Health and Welfare

Principal Investigator

Ogihara Takuo  高崎健康福祉大学, 薬学部, 教授 (80448886)

Co-Investigator(Kenkyū-buntansha) 矢野 健太郎  高崎健康福祉大学, 薬学部, 助教 (40644290)
Co-Investigator(Renkei-kenkyūsha) Arakawa Hiroshi  金沢大学, 医薬保健研究域薬学系, 助教 (40709028)
Idota Yoko  高崎健康福祉大学, 薬学部, 研究員 (90629594)
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
KeywordsP-gp / BCRP / MRPs / 網羅的な阻害 / 足場タンパク / がん組織 / 排出系トランスポーター / 多剤耐性 / MRPs / P-糖たんぱく / MRP / 腎臓がん / 消化管がん / トランスポーター / 組織差 / P-糖タンパク / radixin
Outline of Final Research Achievements

Efflux transporters, as exemplified by P-glycoprotein (P-gp), are localized at the plasma membrane and excrete many therapeutic drugs from the cytoplasm to outside the cells. These transporters are therefore known as a major contributing factor resulting in multidrug resistance of cancer cells. Our study indicated that the regulation of transporters by scaffold proteins, such as ezrin, radixin and moesin (ERM proteins) is different between cancerous tissues. Moreover, these regulatory properties are the same as those of the corresponding normal tissues, and suggest that organ-specific differences in the regulation of P-gp by ERM proteins are retained in cancerous tissues. Furthermore, in tissues such as lung cancer, several efflux transporters were controlled by the same one scaffold protein. Therefore, it was suggested that the suppression of a specific scaffold protein comprehensively inactivated efflux transporters in certain kinds of cancerous tissue.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (32 results)

All 2017 2016 2015 Other

All Journal Article (8 results) (of which Peer Reviewed: 7 results,  Open Access: 4 results,  Acknowledgement Compliant: 3 results) Presentation (22 results) Book (1 results) Remarks (1 results)

  • [Journal Article] Snail-Induced Epithelial-to-Mesenchymal Transition Enhances P-gp-Mediated Multidrug Resistance in HCC827 Cells2017

    • Author(s)
      Tomono Takumi、Yano Kentaro、Ogihara Takuo
    • Journal Title

      Journal of Pharmaceutical Sciences

      Volume: 106 Issue: 9 Pages: 2642-2649

    • DOI

      10.1016/j.xphs.2017.03.011

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Gastrointestinal Hormone Cholecystokinin Increases P-Glycoprotein Membrane Localization and Transport Activity in Caco-2 Cells2017

    • Author(s)
      Yano Kentaro、Shimizu Saori、Tomono Takumi、Ogihara Takuo
    • Journal Title

      Journal of Pharmaceutical Sciences

      Volume: 106 Issue: 9 Pages: 2650-2656

    • DOI

      10.1016/j.xphs.2017.04.003

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effect of Phosphate Binder on the Intestinal Absorption of Antihypertensive Drugs2017

    • Author(s)
      K. Yano, T. Tomono, M. Kanagawa, S. Akiyama, T. Ogihara
    • Journal Title

      J Community Pharm. Pharm. Sci.

      Volume: 9 Pages: 239-245

    • NAID

      40021403150

    • Related Report
      2017 Annual Research Report
  • [Journal Article] Different Regulation of P-Glycoprotein Function between Caco-2 and Caki-1 cells by ERM proteins2016

    • Author(s)
      Yano K, Otsuka K, Kato Y, Kawabata H, Ohmori S, Arakawa H, Ogihara T.
    • Journal Title

      J Pharm Pharmacol.

      Volume: 68 Issue: 3 Pages: 361-367

    • DOI

      10.1111/jphp.12525

    • Related Report
      2016 Research-status Report 2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Adenovirus vector infection of non-small-cell lung cancer cells is a trigger for multi-drug resistance mediated by P-glycoprotein2016

    • Author(s)
      T. Tomono, M. Kajita, K. Yano, T. Ogihara
    • Journal Title

      Biochem. and Biophys. Res. Commun.

      Volume: 476(4) Issue: 4 Pages: 183-187

    • DOI

      10.1016/j.bbrc.2016.05.070

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Interaction of Peptide Transporter 1 With d-Glucose and l-Glutamic Acid; Possible Involvement of Taste Receptors.2016

    • Author(s)
      Arakawa H, Ohmachi T, Ichiba K, Kamioka H, Tomono T, Kanagawa M, Idota Y, Hatano Y, Yano K, Morimoto K, Ogihara T.
    • Journal Title

      J Pharm Sci.

      Volume: 105 Issue: 1 Pages: 339-342

    • DOI

      10.1016/j.xphs.2015.11.024

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Possible interaction of quinolone antibiotics with peptide transporter 1 in oral absorption of peptide-mimetic drugs.2016

    • Author(s)
      Arakawa H, Kamioka H, Kanagawa M, Hatano Y, Idota Y, Yano K, Morimoto K, Ogihara T.
    • Journal Title

      Biopharm Drug Dispos.

      Volume: 37 Issue: 1 Pages: 39-45

    • DOI

      10.1002/bdd.1999

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Recommended Daily Dose of Sesame Lignans Has No Influence on Oral Absorption of P-Glycoprotein Substrates in Rats2015

    • Author(s)
      Tomono T, Otsuka K, Yano K, Kanagawa M, Arakawa H, Ogihara T.
    • Journal Title

      Biological and Pharmaceutical Bulletin

      Volume: 38 Issue: 12 Pages: 1960-1963

    • DOI

      10.1248/bpb.b15-00392

    • NAID

      130005112643

    • ISSN
      0918-6158, 1347-5215
    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] HDAC阻害薬EntinostatはEMTに伴うP-gpの機能亢進を抑制する2017

    • Author(s)
      町田幸也, 伴野拓巳, 矢野健太郎, 荻原琢男
    • Organizer
      日本薬剤学会 第32年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 上皮間葉転換によるP-糖タンパク質の機能亢進は肺がん細胞の薬剤耐性能を増強する2017

    • Author(s)
      上岡宏規, 伴野拓巳, 矢野健太郎, 荻原琢男
    • Organizer
      第12回トランスポーター研究会年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 消化管ホルモンであるコレシストキニンによるP-糖タンパク質の細胞膜上発現および輸送機能の亢進2017

    • Author(s)
      矢野健太郎, 渡邊弥生, 伴野拓巳, 荻原琢男
    • Organizer
      第12回トランスポーター研究会年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] P-糖タンパクを介した薬物の脳内移行性の制御 ; OseltamivirとCilnidipineの例2017

    • Author(s)
      荻原琢男, 森本かおり, 井戸田陽子, 小山智志, 矢野健太郎
    • Organizer
      第39回生体膜と薬物の相互作用シンポジウム
    • Related Report
      2017 Annual Research Report
  • [Presentation] Brain Distribution of Spermine, a Neuromodulator, and Change in the Translocation by Breast Cancer Resistance Protein2017

    • Author(s)
      K. Yano, Y. Yokozuka, E. Matsumoto, S. Koyama, T. Ogihara
    • Organizer
      32nd JSSX Annual Meeting
    • Related Report
      2017 Annual Research Report
  • [Presentation] Snail-induced Epithelial to Mesenchymal Transition Activates P-gp via Increasing the Scaffolding Protein Moesin2017

    • Author(s)
      T. Tomono, H. Kamioka, Y. Shibasaki, S. Koyama, K. Yano, T. Ogihara
    • Organizer
      32nd JSSX Annual Meeting
    • Related Report
      2017 Annual Research Report
  • [Presentation] Effect of Epithelial-Mesenchymal Transition Induced by Snail on Efflux Transporters2017

    • Author(s)
      I. Todokoro, T. Tomono, H. Kamioka, S. Koyama, K. Yano, T. Ogihara
    • Organizer
      32nd JSSX Annual Meeting
    • Related Report
      2017 Annual Research Report
  • [Presentation] The organ-specific regulation of BCRP and P-gp2017

    • Author(s)
      C. Okabe, K. Yano, K. Fujii, Y. Kato, S. Koyama, T. Ogihara
    • Organizer
      32nd JSSX Annual Meeting
    • Related Report
      2017 Annual Research Report
  • [Presentation] 消化管ホルモンであるコレシストキニンによるP-gp機能調節2016

    • Author(s)
      矢野健太郎、清水里織、荻原琢男
    • Organizer
      日本薬物動態学会第31年会
    • Place of Presentation
      松本
    • Year and Date
      2016-10-13
    • Related Report
      2016 Research-status Report
  • [Presentation] BCRPを介した脳興奮物質であるSpermineの排出2016

    • Author(s)
      横塚弥衣、松本映子、矢野健太郎、荻原琢男
    • Organizer
      日本薬物動態学会第31年会
    • Place of Presentation
      松本
    • Year and Date
      2016-10-13
    • Related Report
      2016 Research-status Report
  • [Presentation] Snail過剰発現によるP-gp機能亢進におけるCaveolin-1リン酸化の関与2016

    • Author(s)
      伴野拓巳、矢野健太郎、荻原琢
    • Organizer
      日本薬物動態学会第31年会
    • Place of Presentation
      松本
    • Year and Date
      2016-10-13
    • Related Report
      2016 Research-status Report
  • [Presentation] 肺がん細胞へのリチウム処理によるMRPファミリーの機能変動2016

    • Author(s)
      柴﨑由実、伴野拓巳、矢野健太郎、荻原琢男
    • Organizer
      第60回日本薬学会関東支部大会
    • Place of Presentation
      東京
    • Year and Date
      2016-09-17
    • Related Report
      2016 Research-status Report
  • [Presentation] 非小細胞性肺がん細胞へのアデノウイルス感染がBCRPおよびMRPファミリーに及ぼす影響2016

    • Author(s)
      伴野拓巳, 矢野健太郎, 荻原琢男
    • Organizer
      第11回トランスポーター研究会年会
    • Place of Presentation
      京都
    • Year and Date
      2016-07-02
    • Related Report
      2016 Research-status Report
  • [Presentation] Snail過剰発現によるEMTはHCC827細胞におけるBCRPの発現を低下させる2016

    • Author(s)
      伴野拓巳, 矢野健太郎, 荻原琢男
    • Organizer
      日本薬剤学会第31年会
    • Place of Presentation
      岐阜
    • Year and Date
      2016-05-19
    • Related Report
      2016 Research-status Report
  • [Presentation] 肺腺がん細胞へのアデノウイルス感染はAktのリン酸化を介してP-gpの発現を亢進する2016

    • Author(s)
      柴﨑由実, 伴野拓巳, 矢野健太郎, 荻原琢男
    • Organizer
      日本薬剤学会第31年会
    • Place of Presentation
      岐阜
    • Year and Date
      2016-05-19
    • Related Report
      2016 Research-status Report
  • [Presentation] ヒト腎臓がん細胞のP-gp およびMRPs 輸送機能における足場タンパクの関与2016

    • Author(s)
      加藤 木綿子、矢野 健太郎、井戸田 陽子、荒川 大、荻原 琢男
    • Organizer
      日本薬学会第136年会
    • Place of Presentation
      横浜
    • Year and Date
      2016-03-26
    • Related Report
      2015 Research-status Report
  • [Presentation] 基質薬物とキノロン系抗菌薬との消化管吸収過程における相互作用2015

    • Author(s)
      荻原 琢男、上岡 宏紀、金川 雅彦、井戸田 陽子、矢野 健太郎、森本 かおり、荒川 大
    • Organizer
      第37回生体膜と薬物の相互作用シンポジウム
    • Place of Presentation
      熊本
    • Year and Date
      2015-11-19
    • Related Report
      2015 Research-status Report
  • [Presentation] Tissue-selective regulation of P-gp function in cancers by ERM proteins2015

    • Author(s)
      矢野 健太郎、大塚 杏磨、加藤 木綿子、井戸田 陽子、荒川 大、荻原 琢男
    • Organizer
      日本薬物動態学会第30年会
    • Place of Presentation
      東京 タワーホール船堀
    • Year and Date
      2015-11-12
    • Related Report
      2015 Research-status Report
  • [Presentation] Utility of three-dimensional culture of human hepatocyte as a tool of drug metabolizing enzyme induction2015

    • Author(s)
      荒川 大、上岡 宏紀、井戸田 陽子、矢野 健太郎、荻原 琢男
    • Organizer
      日本薬物動態学会第30年会
    • Place of Presentation
      東京 タワーホール船堀
    • Year and Date
      2015-11-12
    • Related Report
      2015 Research-status Report
  • [Presentation] Transcriptional factor Snail activates P-glycoprotein function in lung adenocarcinoma cells2015

    • Author(s)
      伴野 拓巳、矢野 健太郎、荒川 大、荻原 琢男
    • Organizer
      日本薬物動態学会第30年会
    • Place of Presentation
      東京 タワーホール船堀
    • Year and Date
      2015-11-12
    • Related Report
      2015 Research-status Report
  • [Presentation] 日米EU3局の薬物相互作用ガイドラインの概要まとめと比較2015

    • Author(s)
      山田 浩行、荒川 大、楠本 久美子、小島 肇、荻原 琢男
    • Organizer
      第59回日本薬学会関東支部大会
    • Place of Presentation
      船橋
    • Year and Date
      2015-09-12
    • Related Report
      2015 Research-status Report
  • [Presentation] がん組織におけるERMタンパクによるP-gp輸送機能の調節機構2015

    • Author(s)
      加藤木綿子、矢野健太郎、大塚杏磨、荒川大、荻原琢男
    • Organizer
      第8回トランスポーター研究会
    • Place of Presentation
      慶応義塾大学薬学部
    • Year and Date
      2015-06-20
    • Related Report
      2015 Research-status Report
  • [Book] 実践製剤学-そしてその基礎となる物理薬剤学2015

    • Author(s)
      安藤英紀,飯村菜穂子,石田竜弘,井戸田陽子,荻原琢男
    • Total Pages
      519
    • Publisher
      京都廣川書店
    • Related Report
      2015 Research-status Report
  • [Remarks] 高崎健康福祉大学薬学部教員紹介≪荻原琢男≫

    • URL

      http://www.takasaki-u.ac.jp/p_yaku/1581/

    • Related Report
      2016 Research-status Report

URL: 

Published: 2015-04-16   Modified: 2019-03-29  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi