Sevoflurane affect one of DNA modification?

• Project/Area Number: 16K10932
• 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: Yuko Konishi 名古屋大学, 医学系研究科, 寄附講座助教 (60771970)
• Project Period (FY): 2016-04-01 – 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 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: セボフルラン / 結腸がん細胞株 / 大腸がん細胞株 / がん細胞株 / 吸入麻酔薬 / クロマチンヒストン修飾

Outline of Final Research Achievements

From the growing in vitro evidences suggests that sevoflurane potentially plays a role in the progression of tumors. In this study we revealed that sevoflurane potentially induced one of colorectal cancer cell line through MAPK and Wnt/β-catenin canonical pathway activation. Whereas two of our established Wnt knock out clones undo this proliferation and reduced the number of colonies after 2 weeks in regular culture. These suggested that Wnt genes that comprise a family of secreted lipid-modified signaling glycoprotein were one of key regulator after sevoflurane induced cell growth. To furthew explore we hypothesized that a potential of methylation would occur onto Wnt suppressor genes upon sevoflurane exposure, supporting the our found lower expressed those of suppressor genes. In the contrast our study could not revealed that sevoflurane potentially methylated DNA and lead to reduce the expression such as JMJD Wnt suppressor gene.

Academic Significance and Societal Importance of the Research Achievements

吸入麻酔薬が低酸素などの状況で心筋や神経の保護作用があることが古くから知られているが、一方で癌の再発への影響を精査した実験はまだ十分ではない。本研究ではセボフルラン暴露によって加速した細胞増殖能を、ある遺伝子の欠失クローンを樹立して厳密に比較し基礎データを蓄積することができた。これにより担癌患者へのより適切な麻酔薬の選択に資する基礎データの蓄積を可能にした。将来的には原発癌腫やその遺伝的特性に対応した周術期の麻酔薬を選択することができると考える。

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): Yuko Konishi
  • 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, Zhou Rui, Takahiro Hirai, Tomoko Hayashi, Kanako Ozeki, Nozomi Nakamura, Akiko Akane, Kimitoshi Nishiwaki
  • Organizer: ANESTHESIOLOGY annual meeting
  • Int'l Joint Research
• [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 (ASA)
  • 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、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] 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): 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] 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
• [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
• [Presentation] Sevoflurane stimulates MAPK1/3 phosphorylation after its exposure and caused short cell growth on HCT116 (2016)
  • Author(s): Yuko Konishi, Takahiro Hirai and Kimitoshi Nishiwaki
  • Organizer: The 4th Global Conference on the Perioperative Care of the Cancer Patient
  • Place of Presentation: London, England
  • Year and Date: 2016-11-23
  • Int'l Joint Research
• [Presentation] 各種ヒトがん細胞に与えるセボフルラン暴露影響の予備的研究 (2016)
  • Author(s): 平井 昂宏、小西裕子、西脇公俊
  • Organizer: 日本麻酔科学会 第63回学術集会
  • Place of Presentation: 福岡国際会議場（福岡県福岡市）
  • Year and Date: 2016-05-26
• [Presentation] セボフルランのヒト大腸がん細胞株へ及ぼす影響１―HCT116におけるS期細胞増加について― (2016)
  • Author(s): 小西裕子、平井昂宏、水野祥子、西脇公俊
  • Organizer: 日本麻酔科学会 第63回学術集会
  • Place of Presentation: 福岡国際会議場（福岡県福岡市）
  • Year and Date: 2016-05-26
• [Presentation] セボフルランのヒト大腸がん細胞株へ及ぼす影響２ －HCT116トランスクリプトーム解析－ (2016)
  • Author(s): 小西裕子、水野祥子、平井昂宏、西脇公俊
  • Organizer: 日本麻酔科学会 第63回学術集会
  • Place of Presentation: 福岡国際会議場（福岡県福岡市）