PI polyamide combined with carcinostatic as radiosensitizer

• Project/Area Number: 17K16488
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Radiation science
• Research Institution: Nihon University
• Principal Investigator: ISHIBASHI Naoya 日本大学, 医学部, 准教授 (40649331)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: 抗がん剤結合PIポリアミド / 放射線増感剤 / 放射線治療 / 放射線治療生物学

Outline of Final Research Achievements

We combined PI polyamide with the platinum complex which is an anticancer drug cisplatinum analog as the radiosensitizer.Synthesized PIP-Pt 31-H or 31-Me were applied to tumor cells at a final concentration of from 1pM to 10mM and the cells were exposed to from 1Gy to 10Gy.The radiation sensitizing effect were confirmed by the cell viability rate by WST assay and the colony forming ability by colony formation assay.The cells treated with PIP-Pt tended to lower viability compared with non-treated group in WST assay and colony formation assay.

Academic Significance and Societal Importance of the Research Achievements

放射線治療の効果を高める放射線増感剤は、腫瘍細胞への選択性・特異性の低さや細胞毒性による副作用の問題から一般的に臨床応用されているものはない。本研究では、核DNAに配列特異的に結合する性質を持つPIポリアミド分子に対し、既存の抗がん剤である白金製剤cisplatinの類似白金錯体 (Pt) を結合したPIP-Ptを合成し、放射線照射による核DNA損傷を低濃度で効率的に増強させる放射線増感剤の開発を試みた。
PtをPIポリアミドと結合させることにより放射線による効率的な核DNA損傷を引き起こした可能性がある。