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Novel therapeutic strategy for scirrhous gastric cancer using farnesyltransferase inhibitor

Research Project

Project/Area Number 17K16568
Research Category

Grant-in-Aid for Young Scientists (B)

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

Principal Investigator

Tanaka Tomokazu  佐賀大学, 医学部, 助教 (60781903)

Project Period (FY) 2017-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2018: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywordsファルネシル転換酵素阻害薬 / HIF-1α / 腹膜播種 / 胃癌 / 癌 / ファルネシル化
Outline of Final Research Achievements

Scirrhous gastric cancer causing peritoneal dissemination frequently has extremely high malignant potential and resistance to treatment, therefore the development of new treatment for scirrhous gastric cancer is still desirable. In this study, we examined the anti-tumor effect of farnesyltransferase inhibitor (FTI) and its mechanism of action as a novel therapeutic strategy for scirrhous gastric cancer. FTI suppressed proliferation and migration of gastric cancer cells. Of note, FTI showed stronger anti-tumor effect on gastric cancer cells with HIF1-α high expression (HIF1-α high expression = high malignant potential). The same results were verified in animal experiments. As the mechanism of anti-tumor effect, FTI inhibited HIF1-α expression, and also suppressed mTOR pathway (a kind of signal transduction pathway involved in cancer growth) and the production of reactive oxygen species.

Academic Significance and Societal Importance of the Research Achievements

本研究の成果(FTIのHIF1-α高発現胃癌細胞に対する抗腫瘍効果)によって、難治性転移様式である胃癌腹膜播種を発症した患者に対する新たな治療方法の選択肢となり得る可能性がある。また、腹膜播種を高率に発症するような高悪性度のHIF1-α高発現胃癌細胞にこそ治療効果が期待でき、腹膜播種再発の予防としての効果も期待できる。さらには、HIF1-α高発現は、ほとんどの固形癌に共通する高悪性度の指標であることから、FTIの治療効果は胃癌細胞のみならず、HIF1-α高発現であれば他の固形癌においても治療効果が期待できる可能性がある。

Report

(3 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • Research Products

    (3 results)

All 2018 2017

All Presentation (3 results)

  • [Presentation] 胃癌治療におけるファルネシル転移酵素阻害薬の可能性2018

    • Author(s)
      江川紀幸
    • Organizer
      第77回日本癌学会学術総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Farnesyltransferase inhibitorsはHIF-1α発現胃癌細胞株に対して抗腫瘍効果を示す2018

    • Author(s)
      江川紀幸
    • Organizer
      第119回日本外科学会定期学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 胃癌治療におけるファルネシル転移酵素阻害薬の可能性2017

    • Author(s)
      江川紀幸
    • Organizer
      日本癌学会
    • Related Report
      2017 Research-status Report

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Published: 2017-04-28   Modified: 2020-03-30  

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