Development of cancer treatment targeting morphogen and cancer stem cell

• Project/Area Number: 24592043
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Kawasaki Medical School
• Principal Investigator: NAKAMURA Masafumi 川崎医科大学, 医学部, 教授 (30372741)
• Co-Investigator(Kenkyū-buntansha): NAKASHIMA Hiroshi 川崎医科大学, 医学部, 講師 (60623048) ; TSUTSUMI Kosuke 川崎医科大学, 医学部, 助教 (00467937)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2012: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: 膵癌 / 癌微小環境 / 形態形成シグナル / Hedgehog signaling / Sonic Hedgehog / metformin / AMPK / Hedgehogシグナル / Sonic Hedgehog (Shh) / 自己抗体 / 癌性幹細胞 / 微小環境 / 線維芽細胞

Outline of Final Research Achievements

[Aim] The aim of this study is to explore the relationship between metformin and Hh signaling pathway, and to clarify the mechanism by which metformin prevents cancers. [Materials and methods] Expression of Shh was examined at protein and mRNA level with or without metformin by real-time PCR, immunoblotting and immunestaining. Phosphorylation of AMPK was detected by immunoblotting. [Results] Shh expression was decreased at protein and mRNA level by addition of metformin in BxPC3 cells. Phosphorylation of AMPK was increased by metformin and decreased by dorsomorphin. Interestingly, Shh expression was increased by dorsomorphin. This effect was further confirmed by siRNA of AMPK. [Conclusion] Metformin inhibits production of Shh in BxPC3 through phosphorylation of AMPK. Activation of AMPK might be one of the routes to link metformin and suppression of Shh.

Research Products

• [Journal Article] Metformin suppresses Sonic Hedgehog expression in pancreatic cancer cells (2014)
  • Author(s): Masafumi Nakamura, Ayako Ogo, Masahiro Yamamura, Yoshiyuki Yamaguchi and Hiroshi Nakashima
  • Journal Title: Anticancer Research Volume: 34 Pages: 1765-1770
  • Peer Reviewed
• [Journal Article] Profiling of Autoantibodies in Sera of Pancreatic Cancer Patients (2014)
  • Author(s): Yosuke Nagayoshi, Masafumi Nakamura, Kazuhiro Matsuoka, Takao Ohtsuka, Yasuhisa Mori, Hiroshi Kono, Teppei Aso, Noboru Ideno, Shunichi Takahata, Akihide Ryo, Hiroyuki Takeda, Tetsuhide Ito, Yoshinao Oda, Yaeta Endo, Tatsuya Sawasaki, Masao Tanaka
  • Journal Title: Annals of surgical oncology Volume: in press
  • Peer Reviewed
• [Journal Article] High expression of microRNA-155 is associated with the aggressive malignant behavior of gallbladder carcinoma (2013)
  • Author(s): Hiroshi Kono, Masafumi Nakamura, Takao Ohtsuka, Yosuke Nagayoshi, Yasuhisa Mori, Shunich Takahata, Shinich Aishima, Masao Tanaka
  • Journal Title: ONCOLOGY REPORTS Volume: in press
  • Peer Reviewed
• [Presentation] 膵・胆管合流異常と胆嚢癌におけるmicroRNA発現解析 (2013)
  • Author(s): 河野博、中村雅史、大塚隆生、藤野稔、田村公二、井手野昇、安蘇鉄平、永吉洋介、上田純二、高畑俊一、小田義直、田中雅夫
  • Organizer: 第１１３回日本外科学会定期学術集会
  • Place of Presentation: 福岡国際会議場（福岡県）
• [Presentation] ビオチン化タンパク質ライブラリーを用いた膵癌患者血中自己抗体プロファイリング
  • Author(s): 永吉洋介, 中村雅史, 松岡和弘, 安蘇鉄平, 井手野昇, 河野博, 大塚隆生, 高畑俊一, 澤崎達也, 田中雅夫
  • Organizer: 第68回日本消化器外科学会総会
  • Place of Presentation: 宮崎市(シーガイアコンベンションセンター)
• [Remarks] 川崎医科大学消化器外科ホームページ
  • URL: http://www.kawasaki-m.ac.jp/dig-surg/index.html