Therapeutic effect of the GSK3beta-inhibiting drugs against gastrointestinal cancer and the elucidation of a molecular mechanism

2013 Fiscal Year Final Research Report

• Project/Area Number: 23591955
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Kanazawa University
• Principal Investigator: HIROSE Mayumi 金沢大学, がん進展制御研究所, 研究員 (00353524)
• Co-Investigator(Kenkyū-buntansha): MINAMOTO Toshinari 金沢大学, がん進展制御研究所, 教授 (50239323) ; KAWAKAMI Kazuyuki 東京女子医科大学, 医学部, 准教授 (00293358)
• Project Period (FY): 2011 – 2013
• Keywords: 消化器がん / 大腸がん / すい臓がん / GSK3beta / Drug repositioning / 医薬品 / 細胞運動

Research Abstract

GSK3beta is a serine/threonine protein kinase that implicated in diseases including cancer. To date, there are no clinical trial reports describing the use of specific GSK3beta inhibitors for cancer, while our results of basic research have identified GSK3beta as a tumor promoter and druggable target for cancer treatment. Several drugs prescribed for diseases other than cancer were shown to have an inhibitory effect against GSK3beta. Here we show that inhibition of GSK3beta by using these drugs, alone or in combination, compromises survival, proliferation, migration and invasion of human colon and pancreatic cancer cells. We also show that the combination of GSK3beta-inhibiting drugs is more effective than the single agent treatment against both types of cancer cell lines. Our findings warrant further investigation and preclinical study on the effective combination of GSK3beta-inhibiting drugs and that with chemotherapeutic agents for treatment of gastrointestinal cancer.

Research Products

• [Journal Article] Glycogen synthase kinase 3beta inhibition sensitizes human glioblastoma cells to temozolomide by affecting O6-methylguanine DNA methyltransferase promoter methylation via c-Myc signaling (2013)
  • Author(s): Pyko IV, Nakada M, Sabit H, Teng L, Furuyama N, Hayashi Y, Kawakami K, Minamoto T, Fedulau AS, Hamada J.
  • Journal Title: Carcinogenesis Volume: 34(10) Pages: 2206-17
  • DOI: 10.1093/carcin/bgt182
  • URL: http://www.kanazawa-u.ac.jp/~ganken/shuyoseigyo/
  • Peer Reviewed
• [Journal Article] Aberrant glycogen synthase kinase 3 beta is involved in pancreatic cancer cell invasion and resistance to therapy (2013)
  • Author(s): Kitano Y., Shimasaki T., Chikano Y., Nakada M., Hirose M., Higashi T., Ishigaki Y., Endo Y., Takino T., Sato H., Sai Y, Miyamoto K., Motoo Y, Minamoto T.
  • Journal Title: PLoS One Volume: 8(2) Pages: e55289
  • DOI: 10.1371/journal.pone.0055289
  • URL: http://www.kanazawa-u.ac.jp/~ganken/shuyoseigyo/
  • Peer Reviewed
• [Journal Article] 5.Glycogen synthase kinase 3beta inhibition sensitizes pancreatic cancer cells to gemcitabine (2012)
  • Author(s): Shimasaki T, Ishigaki Y, Nakamura Y, Takata T, Nakaya N, Nakajima H, Sato I, Zhao X, Kitano A, Kawakami K, Tanaka T, Takegami T, Tomosugi N, Minamoto T, Motoo Y.
  • Journal Title: J Gastroenterol Volume: 47(3) Pages: 321-33
  • DOI: 10.1007/s00535-011-0484-9
  • URL: http://www.kanazawa-u.ac.jp/~ganken/shuyoseigyo/
  • Peer Reviewed
• [Journal Article] Metabolic disorder, inflammation, and deregulated molecular pathways converging in pancreatic cancer development : implications for new therapeutic strategies (2011)
  • Author(s): Motoo Y, Shimasaki T, Ishigaki Y, Nakajima H, Kawakami K, Minamoto T.
  • Journal Title: Cancers (Basel) Volume: 24;3(1) Pages: 446-60
  • DOI: 10.3390/cancers3010446
  • URL: http://www.kanazawa-u.ac.jp/~ganken/shuyoseigyo/
  • Peer Reviewed
• [Presentation] Therapeutic effect of the cocktail of GSK3beta-inhibiting drugs against colon cancer (2014)
  • Author(s): Mayumi Hirose, Takahiro Domoto, Toshinari Minamoto
  • Organizer: 金沢国際がん生物学シンポジウム&アカデミア創薬シンポジウム
  • Place of Presentation: 金沢・エクセル東急
  • Year and Date: 20140123-24
• [Presentation] Therapeutic effect of the GSK3beta-inhibiting drugs against colon cancer:GSK3beta阻害作用を有する医薬品の大腸がんに対する治療効果 (2013)
  • Author(s): Mayumi Hirose, Yumi Ito, Takahiro Domoto , Toshinari Minamoto
  • Organizer: 第72回日本癌学界学術総会
  • Place of Presentation: 横浜・パシフィコ横浜
  • Year and Date: 20131003-05
• [Presentation] Putative pathological role of GSK3beta in aberrant glucose metabolism in colon cancer cells:大腸がん細胞の糖代謝特性におけるGSK3betaの病的作用 (2013)
  • Author(s): Domoto Takahiro1, Mayumi Hirose, Tomoyoshi Soga, Hiroyasu Esumi, Toshinari Minamoto
  • Organizer: 第72回日本癌学界学術総会
  • Place of Presentation: 横浜・パシフィコ横浜
  • Year and Date: 20131003-05
• [Presentation] 大腸がんの糖代謝経路におけるGSK3betaの機能解析 (2013)
  • Author(s): 堂本貴寛、廣瀬まゆみ、紙健次郎、曽我朋義、江角浩安、源利成
  • Organizer: 第24回日本消化器癌発生学会総会
  • Place of Presentation: 金沢・石川県立音楽堂
  • Year and Date: 20130905-06
• [Presentation] 既存医薬品を用いたGSK3beta阻害による大腸がん治療法の開発 (2013)
  • Author(s): 廣瀬まゆみ、堂本貴寛、伊藤友美、源利成
  • Organizer: 第24回日本消化器癌発生学会総会
  • Place of Presentation: 金沢・石川県立音楽堂
  • Year and Date: 20130905-06
• [Presentation] SK3betaを標的とした既存医薬品を用いた大腸がん治療の開発 (2013)
  • Author(s): 廣瀬まゆみ、堂本貴寛、伊藤有美、川上和之、源利成
  • Organizer: 第78回大腸癌研究会
  • Place of Presentation: 東京・都市センターホテル
  • Year and Date: 2013-01-18
• [Remarks] 金沢大学がん進展制御研究所臓器制御研究分野
  • URL: http://www.kanazawa-u.ac.jp/~ganken/shuyoseigyo/
• [Remarks] 金沢大学がん進展制御研究所
  • URL: http://www.kanazawa-u.ac.jp/~ganken/