Elucidation and overcoming of the drug resistance in cancer cells in the presence of the osteoclast.

2013 Fiscal Year Final Research Report

• Project/Area Number: 24890152
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Surgical dentistry
• Research Institution: The University of Tokushima
• Principal Investigator: WATANABE Keiichiro 徳島大学, 大学病院, 助教 (20634554)
• Project Period (FY): 2012-08-31 – 2014-03-31
• Keywords: 癌 / 酸性環境 / 薬剤耐性

Research Abstract

In an acidic environment, myeloma cells sense an acid and activate survival pathways via PI3K-Akt. The activation and survival of the acid-sensitive myeloma cells to enhance the expression of the pH sensor their further the vicious circle enhancing signal is formed has been suggested. Moreover, nuclear translocation of the transcription factor Sp1 in myeloma cells was promoted expression of HDAC and suppressed gene expression of apoptosis-inducing factor DR4 in an acid environment. HDAC inhibitors were allowed to recover for the suppression of the expression of DR4. Therefore, PI3K-Akt inhibitors, and the combination of HDAC inhibitors and DR4 agonist antibody were considered a candidate for therapeutic agents to overcome drug resistance of myeloma cells in an acid environment.

Research Products

• [Presentation] 酸性環境は骨髄腫細胞のDR4の発現をエピジェネティックに抑制しTRAILに対する抵抗性を獲得させる (2013)
  • Author(s): 天知良太、安倍正博、渡邉佳一郎、賀川久美子、藤井志朗、原田武志、三木浩和、中村信元、小田明日香、日浅雅博、田中栄二、松本俊夫
  • Organizer: 第72回日本矯正歯科学会学術集会
  • Place of Presentation: キッセイ文化ホール・松本市総合体育館(長野)
  • Year and Date: 20131007-09
• [Presentation] Acidic conditions epigenetically repress the TRAIL receptor DR4 in myeloma cells to confer their resistance to TRAIL (2013)
  • Author(s): Amachi R, Watanabe K, Fujii S, Harada T, Miki H, Nakamura S , Oda A, Hiasa M, Tanaka E, Matsumoto T, Abe M
  • Organizer: American Society of Bone and Mineral Research 2013
  • Place of Presentation: ボルチモアコンベンションセンター(アメリカ)
  • Year and Date: 20131004-07
• [Presentation] An acidic milieu confers the resistance to TRAIL in myeloma cells through the PI3K-Akt-mediated epigenetic down- regulation of the TRAIL receptor DR4 (2013)
  • Author(s): Amachi R, Watanabe K, Fujii S, Harada T, Miki H, Nakamura S , Oda A, Hiasa M, Tanaka E, Matsumoto T, Abe M
  • Organizer: 2^<nd> Joint Meeting of the IBMS and JSBMR
  • Place of Presentation: 神戸ポートピアホテル(兵庫)
  • Year and Date: 20130528-0601
• [Presentation] An acidic milieu suppresses histone acetylation in myeloma cells to down-regulate the TRAIL receptor DR4 expression (2013)
  • Author(s): Amachi R, Watanabe K, Fujii S, Harada T, Miki H, Nakamura S , Oda A, Hiasa M, Tanaka E, Matsumoto T, Abe M
  • Organizer: 14^<th> International Myeloma Workshop
  • Place of Presentation: 国立京都国際会議場(京都)
  • Year and Date: 20130403-07
• [Presentation] 酸性環境は骨髄腫細胞のDR4の発現をエピジェネティックに抑制しTRAILに対する抵抗性を獲得させる (2013)
  • Author(s): 天知良太、安倍正博、渡邉佳一郎、賀川久美子、藤井志朗、原田武志、三木浩和、中村信元、小田明日香、日浅雅博、田中栄二、松本俊夫
  • Organizer: 癌と骨病変研究会
  • Place of Presentation: 千代田放送会館(東京)
  • Year and Date: 2013-11-18
• [Presentation] An acidic milieu suppresses DR4 editing and induces p22 c-FLIP to cause myeloma resistance to TRAIL (2012)
  • Author(s): Amachi R, AbeM, Watanabe K, Kagawa K, Fujii S, Harada T, Miki H, Nakamura S, Oda A, Hiasa M, Tanaka E, Matsumoto T
  • Organizer: 第74回日本血液学会学術集会
  • Place of Presentation: 国立京都国際会議場(京都)
  • Year and Date: 20121019-21
• [Presentation] 酸性環境は骨髄腫細胞にDR4の発現抑制とcFLIPの活性化を惹起しTRAILに対する抵抗性を獲得させる (2012)
  • Author(s): 天知良太、安倍正博、渡邉佳一郎、中村信元、日浅雅博、田中栄二、松本俊夫
  • Organizer: 第30回骨代謝学会学術集会
  • Place of Presentation: 京王プラザホテル(東京)
  • Year and Date: 20120719-21