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Valproic acid inhibits irradiation-induced epithelial-mesenchymal transition and stem cell-like characteristics in esophageal squamous cell carcinoma

Research Project

Project/Area Number 25461909
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Radiation science
Research InstitutionKanazawa University

Principal Investigator

Itasu Ninomiya  金沢大学, 大学病院, 准教授 (60345618)

Co-Investigator(Kenkyū-buntansha) 藤村 隆  金沢大学, 医学系, 准教授 (50262580)
Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords食道癌 / 放射線治療 / 放射線耐性 / 放射線感受性 / バルプロ酸 / ヒストン脱アセチル化阻害剤 / 上皮間葉転換 / 放射線 / 上皮間葉移行 / HDAC阻害剤 / 放射線照射 / がん幹細胞
Outline of Final Research Achievements

We investigated the mechanism of radio-resistance and the anti-radioresistant and radiosensitizing effect of classic histone deacetylase (HDAC) inhibitor valproic acid (VPA) in esophageal squamous cell carcinoma (ESCC) cells. First, we showed that 2 Gy of irradiation induced epithelial–mesenchymal transition (EMT) and cancer stem-like cell properties in ESCC TE9 cells. In addition, irradiation enhanced invasion and migration ability with upregulation of matrix metalloproteinases. Second, we found that VPA induced reversal of EMT caused by irradiation in TE9 cells, resulting in attenuated cell invasion and migration abilities. Third, VPA induced Ku70 acetylation and prolonged γH2AX levels after irradiation in three ESCC cell lines (KES, TE9, TE10). Our results suggest that VPA inhibit radiation induced EMT and show radiosensitizing effect by inhibiting DNA double strand break repair pathway in ESCC.

Report

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

    (4 results)

All 2016 2015 2014

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (3 results)

  • [Journal Article] Inhibitory effects of valproic acid in DNA double-strand break repair after irradiation in esophageal squamous carcinoma cells.2015

    • Author(s)
      Makita N, Ninomiya I, Tsukada T, Okamoto K, Harada S, Nakanuma S, Sakai S, Makino I, Kinoshita J, Hayashi H, Oyama K, Nakagawara H, Miyashita T, Tajima H, Takamura H, Fushida S, Ohta T
    • Journal Title

      Oncol Rep.

      Volume: 34(3) Issue: 3 Pages: 1185-1192

    • DOI

      10.3892/or.2015.4089

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] 食道癌細胞におけるvalproic acid の放射線照射後DNA二重鎖切断修復阻害効果2016

    • Author(s)
      牧田直樹、二宮 致
    • Organizer
      第116回日本外科学会定期学術集会
    • Place of Presentation
      リーガロイヤルホテル大阪(大阪府・大阪市)
    • Year and Date
      2016-04-14
    • Related Report
      2015 Annual Research Report
  • [Presentation] 食道癌細胞におけるvalproic acid Epithelial to Mesenchymal Transition(EMT)とcancer stem like cell feature抑制効果の検討2014

    • Author(s)
      金本斐子、二宮致
    • Organizer
      第12回日本消化器外科学会大会
    • Place of Presentation
      神戸国際展示場(兵庫県神戸市)
    • Year and Date
      2014-10-23 – 2014-10-26
    • Related Report
      2014 Research-status Report
  • [Presentation] 食道癌細胞におけるvalproic acidの上皮間葉転換抑制効果の検討2014

    • Author(s)
      金本斐子、二宮致
    • Organizer
      第23回日本がん転移学会学術集会・総会
    • Place of Presentation
      金沢市文化ホール(石川県金沢市)
    • Year and Date
      2014-07-10 – 2014-07-11
    • Related Report
      2014 Research-status Report

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

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