Efficacy of newly developed platinum complexes against osteosarcoma, bone targeting platinum and proteasome inhibitory platinum.

• Project/Area Number: 23592180
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: Kanazawa University
• Principal Investigator: YAMAMOTO Norio 金沢大学, 医薬保健学総合研究科, 特任教授 (90332668)
• Project Period (FY): 2011-04-28 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2011: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000)
• Keywords: 新規プラチナ製剤 / 骨肉腫 / 蛍光タンパク遺伝子導入細胞 / 抗がん剤 / 新規開発 / プラチナ製剤

Outline of Final Research Achievements

Each compound strongly caused concentration-dependent cytocidal effect. IC50 value of trinuclear compound is superior to cisplatin, and both complexes showed caffeine potentiation. Two novel platinum do not show cross resistance to cisplatin. Apoptosis induction and acetylation of histon H2AX were observed. In vivo, 1Pt showed almost same, 3Pt showed stronger antitumor effect compared to cisplatin.Two novel platinum complexes that we developed showed strong ant-tumor effect in osteosarcoma in vitro and in vivo. 3Pt shows superior anti-tumor effect compared to cisplatin. 1Pt shows strong in vivo anti-tumor activity. Apoptosis is induced by DNA double strand break. Novel platinum compounds may overcome cisplatin resistance.

Research Products

• [Presentation] Novel platinum complex effective against osteosarcoma, bone targeting platinum and proteasome inhibitory platinum (2013)
  • Author(s): Kentaro Igarashi, Norio Yamamoto, Toshiharu Shirai, Hideji Nishida, Katsuhiro Hayashi, Yoshikazu Tanzawa, Hiroaki Kimura, Akihiko Takeuchi, Shinji Miwa, Hiroyuki Inatani, Shingo Shimozaki, Takashi Kato, Akira Odani, Hiroyuki Tsuchiya
  • Organizer: 2013 Annual Meeting of American Academy of Orthopaedic Surgeons
  • Place of Presentation: Chicago， USA
• [Presentation] 新規プラチナ製剤の骨肉腫細胞株に対する抗腫瘍効果 (2011)
  • Author(s): 五十嵐健太郎、山本憲男、小谷明、土屋弘行
  • Organizer: がん治療学会
  • Place of Presentation: 愛知県（国際会議場）
• [Presentation] Novel platinum complexes effective against osteosarcoma cell lines (2011)
  • Author(s): K. Igarashi, N. Yamamoto, A. Odani, H. Tsuchiya
  • Organizer: ISOLS
  • Place of Presentation: 中国（北京コンベンションセンター）