2021 Fiscal Year Final Research Report

Efficacy and toxicity of bladder instillation of anti-tumor peptide for inhibition of bladder tumor in mice

Research Project

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Project/Area Number	19K09683
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Review Section	Basic Section 56030:Urology-related
Research Institution	University of Tsukuba
Principal Investigator	Shimazui Toru 筑波大学, 医学医療系, 客員研究員 (80235613)
Co-Investigator(Kenkyū-buntansha)	西山博之筑波大学, 医学医療系, 教授 (20324642) 小島崇宏愛知県がんセンター(研究所), 腫瘍制御学分野, 研究員 (40626892) 吉川和宏愛知医科大学, 公私立大学の部局等, 特務教授 (60109759)
Project Period (FY)	2019-04-01 – 2022-03-31
Keywords	膀胱腫瘍 / 機能性ペプチド / p16 / p14 / p19 / 膀胱移植モデル / 膀胱注入 / 毒性試験
Outline of Final Research Achievements	Retinoblastoma (Rb) protein pathway is key molecules of bladder tumor (BT) development, and Rb dysfunction is associated with p16 or p14 to p53 pathway. Here, we evaluate the efficacy and toxicity of peptide administration for mouse p16 and mouse p19, which is homology of human p14, on mouse bladder implantation model for using p16- and p19-abscent mouse BT cell line. MB49 bladder implantation tumor was inhibited by peptide transduction by bladder instillation of peptides, for 0% to 9.1% of BT development in peptide groups as compared with 76.9% of control group. Papillary epithelium was frequently observed in peptide groups, whereas no Ki-67 labelling indicated different from tumor profile. No hematological and histological organ toxicity was observed in systemic administration of p16 or p19 peptides in mice.
Free Research Field	泌尿器科腫瘍
Academic Significance and Societal Importance of the Research Achievements	膀胱癌は膀胱を温存して治療する場合、経尿道的切除が行われるが、切除後の癌細胞の再生着による膀胱再発が多く、抗癌剤やBCGの膀胱注入による予防が標準的であるが、効果の限界や強い副作用、抵抗性などの課題がある。本研究で膀胱癌の発生・進展にかかわる分子の異常を修復しうるペプチドの膀胱注入が膀胱腫瘍の発生を抑制しうることを動物モデルで示したことは、今後、膀胱注入による分子標的治療のひとつと考えられ、新たな治療選択肢として発展していくことが期待される。