sevoflruane may affect cancer cell proliferation through Wnt signaling

• Project/Area Number: 17K11048
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Anesthesiology
• Research Institution: Nagoya University
• Principal Investigator: Hayashi Tomoko 名古屋大学, 医学系研究科, 招へい教員 (10718414)
• Co-Investigator(Kenkyū-buntansha): 小西 裕子 名古屋大学, 医学系研究科, 寄附講座助教 (60771970)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: ヒトがん細胞株 / セボフルラン / 吸入麻酔薬 / がん細胞株 / 足場非依存性増殖 / 浸潤 / がん細胞

Outline of Final Research Achievements

Volatile anesthesias have been reported protect myocardial tissue against reperfusion injury on myocardial ischaemia and kidney disturbance. Surgical treated cancer cells potentially influenced similar protection in the perioperative period. We recently showed one of a volatile anesthesia sevoflurane induced the growth on some of cancer cell lines as context independent manner. In this studied we revealed that sevoflurane induced Wnt/β-catenin canonical pathway accompanied with MAPK activation by established Wnt knock out clones derived from human colorectal cancer cell line. These clones also revealed that one of Wnts gene is necessary for anchorage independent growth and colonization growth post its exposure of clinical relevant dosed sevoflurane. Above all we clarified that sevoflurane onwards the Wnt/β-catenin pathway and maintain its growth to one of human colon cancer cell line.

Academic Significance and Societal Importance of the Research Achievements

本研究では大腸がんの初期に関わるとされるWnt/β-catenin経路がセボフルラン暴露により活性化し、一部のヒト培養細胞株で長期的な増殖能を高めることを確認した。しかし本研究は実験室での培養細胞株を主に使用した研究であるため、より生体に近い環境での詳細な検討が必須である。本研究により、将来的に各癌腫に応じた麻酔薬の選択に資する厳密な基礎研究の一部を達成することができた。

Research Products

• [Journal Article] Differential effects of sevoflurane on the growth and apoptosis of human cancer cell lines (2019)
  • Author(s): Takahiro Hirai, Yuko Konishi, Shoko Mizuno, Zhou Rui, Yao Sun, Kimitoshi Nishiwaki
  • Journal Title: Journal of Anesthesia Volume: 34 Issue: 1 Pages: 47-57
  • DOI: 10.1007/s00540-019-02701-w
  • NAID: 40022158057
  • Peer Reviewed / Open Access
• [Presentation] Low-dose sevoflurane induces human cancer cell line proliferation along with ERK and AKT phosphorylation in vitro and in vivo (2019)
  • Author(s): 小西裕子
  • Organizer: 日本麻酔科学会 第66回学術集会
  • Invited
• [Presentation] Low Dose Sevoflurane Induced Colon Cancer Cell Growth Accompanied with ERK and AKT Phosphorylation in Vitro (2019)
  • Author(s): Yuko Konishi, Takahiro Hirai, Tomoko Hayashi, Kanako Ozeki, Nozomi Nakamura, Akiko Akane, Kimitoshi Nishiwaki
  • Organizer: American Society of Anesthesiologists
  • Int'l Joint Research
• [Presentation] 吸入麻酔薬セボフルラン暴露後にヒトがん培養細胞株が示す増殖能の変化 (2018)
  • Author(s): 小西裕子（発表者）、周睿、林智子、平井昂宏、西脇公俊
  • Organizer: 第59回日本肺癌学会学術集会
• [Presentation] . 1% Sevoflurane exposure is associated with early and late apoptotic cell death onA549 and MCF-7 cell lines (2018)
  • Author(s): Takahiro Hirai YK, and Kimitoshi Nishiwaki
  • Organizer: American Society of Anesthesiologists
  • Int'l Joint Research
• [Presentation] ヒト大腸がん細胞株を用いたセボフルラン暴露と足場非依存性増殖能の検討（優秀演題） (2017)
  • Author(s): 小西裕子、周睿、平井昂宏、西脇公俊
  • Organizer: 日本麻酔科学会 第64回学術集会
• [Presentation] セボフルラン暴露後に生じる大腸癌細胞株の短期的な増殖はERK1/2のリン酸化が関与する (2017)
  • Author(s): 平井昂宏、小西裕子、周睿、西脇公俊
  • Organizer: 日本麻酔科学会 第64回学術集会
• [Presentation] Sevoflurane partly promotes cancer cell growth (2017)
  • Author(s): Yuko Konishi, Takahiro Hirai, Sachiko Mizuno and Kimitoshi Nishiwaki
  • Organizer: 5th Global Conference on Perioperative Care of the Cancer Patient
  • Int'l Joint Research
• [Presentation] Sevoflurane stimulates MAPK1/3 phosphorylation after its exposure and caused short cell growth on HCT116 (2017)
  • Author(s): Takahiro Hirai, Yuko Konishi and Kimitoshi Nishiwaki
  • Organizer: ASA; American Society of Anesthesiologists
  • Int'l Joint Research