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Establishment of novel drug therapy targetting Warburg effect in gastric cancer

Research Project

Project/Area Number 25462025
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Digestive surgery
Research InstitutionSaga University

Principal Investigator

Kitajima Yoshihiko  佐賀大学, 医学部, 客員研究員 (30234256)

Co-Investigator(Kenkyū-buntansha) NAKAMURA Jun  佐賀大学, 医学部, 助教 (60404175)
Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
KeywordsHIF-1α / 胃癌 / ワールブルグ効果 / グルコース / インスリン / 活性酸素 / アポトーシス / HIF-1a / 低酸素環境 / 治療モデル / Warburg効果 / HIF-1 / 低酸素刺激
Outline of Final Research Achievements

Hypoxia is substantial in solid tumors. Cancer cells under hypoxic environment are known to increase malignant characters including matastasis and drug resistance. Present study revealed that HIF-1α knockdown (KD) destroyed Warburg effect in gastric cancer cell line 58As9 under hypoxia, and induced apoptosis owing to excessive ROS production. Glucose (G) plus Insulin (I) treatment enhanced the apoptotic effect in the hypoxic 58As9 KD cells due to further ROS production. In vivo study showed that GI treatment increased apoptotic cells of 58As9 KD tumor, but not 58As9 control in nude mice, supporting in vitro data.
These results was successfully published in PLoS One paper in 2015. Thereafter, we isolated HIF-1α inhibitor YC-1 and revealed that YC-1 + GI therapy induced apoptotic effect in wild type 58As9 cells under hypoxia. At present, we are investigating whether or not YC-1 + GI therapy provides apoptotic effect on 58As9 tumor in nude mice.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • 2013 Research-status Report
  • Research Products

    (8 results)

All 2015 2014 2013

All Journal Article (2 results) (of which Peer Reviewed: 2 results,  Open Access: 1 results) Presentation (6 results)

  • [Journal Article] The apoptotic effect of HIF-1α inhibition combined with glucose plus insulin treatment on gastric cancer under hypoxic conditions2015

    • Author(s)
      Tanaka T, Kitajima Y, Miyake S et al
    • Journal Title

      PLoS One

      Volume: 10

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] HIF-1a is a crucial factor in the development of peritoneal dissemination via natural metastatic rouites in scirrhous gastric cancer2013

    • Author(s)
      Miyake S, Kitajima Y, Nakamura J, Kai K, Yanagihara K et al
    • Journal Title

      Int J Oncol

      Volume: 43 Issue: 5 Pages: 1431-1440

    • DOI

      10.3892/ijo.2013.2068

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] 固形癌の低酸素環境下エネルギー代謝変容に着眼したHIF-1α阻害剤+GI療法の機序解析と臨床応用への可能性2015

    • Author(s)
      脇山幸大、北島吉彦、三宅修輔 他
    • Organizer
      第3回がんと代謝研究会
    • Place of Presentation
      金沢
    • Year and Date
      2015-07-16
    • Related Report
      2015 Annual Research Report
  • [Presentation] HIF-1αと癌エネルギー代謝変容に着眼した新規胃癌治療の可能性2015

    • Author(s)
      脇山幸大、北島吉彦、田中智和 他
    • Organizer
      第115回日本外科学会定期学術集会
    • Place of Presentation
      名古屋
    • Year and Date
      2015-04-16
    • Related Report
      2015 Annual Research Report
  • [Presentation] HIF-1a発現阻害+GI療法は胃癌に対する理想的薬物治療となりうる2014

    • Author(s)
      脇山幸大、北島吉彦、田中智和、三宅修輔、西島亜紀、柳原五吉他
    • Organizer
      第73回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2014-09-25 – 2014-09-27
    • Related Report
      2014 Research-status Report
  • [Presentation] 低酸素環境下のエネルギー代謝変容に着眼した新たな胃癌薬物治療の可能性2014

    • Author(s)
      北島吉彦、田中智和、三宅修輔、中村 淳、宮崎耕治、能城浩和
    • Organizer
      第2回がんと代謝研究会
    • Place of Presentation
      東京理科大葛飾キャンパス
    • Year and Date
      2014-07-10 – 2014-07-11
    • Related Report
      2014 Research-status Report
  • [Presentation] Warburg効果をターゲットとした新たな胃癌薬物治療の可能性2013

    • Author(s)
      田中智和、北島吉彦、三宅修輔、柳原五吉、馬場耕一、志田雅明 他
    • Organizer
      第24回日本消化器癌発生学会
    • Place of Presentation
      石川県立音楽堂
    • Related Report
      2013 Research-status Report
  • [Presentation] スキルス胃癌の腹膜播種はHIF-1あにより活性化されるリンパ管新生を介した遠隔転移である2013

    • Author(s)
      三宅修輔、北島吉彦、中村 淳、柳原五吉、田中智和、馬場耕一 他
    • Organizer
      第24回日本消化器癌発生学会
    • Place of Presentation
      石川県立音楽堂
    • Related Report
      2013 Research-status Report

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Published: 2014-07-25   Modified: 2019-07-29  

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