Basic research of PARP inhibitor effects for chemotherapy induced mucositis

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K10196
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 57060:Surgical dentistry-related
• Research Institution: Tsurumi Junior College
• Principal Investigator: Fujihara Hisako 鶴見大学短期大学部, 歯科衛生科, 教授 (80396746)
• Co-Investigator(Kenkyū-buntansha): 熊谷 賢一 東京大学, 医学部附属病院, 助教 (10518129) ; 川口 浩司 鶴見大学, 歯学部, 准教授 (50277951) ; 濱田 良樹 鶴見大学, 歯学部, 教授 (70247336) ; 大島 朋子 鶴見大学, 歯学部, 教授 (50233101) ; 伊藤 由美 鶴見大学, 歯学部附属病院, 講師 (00176372)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: PARP阻害剤 / CDDP / 抗腫瘍薬誘発障害 / 菌叢解析

Outline of Final Research Achievements

In this study, the systemic effects of the anti-tumour drug CDDP and the molecularly targeted drug PARP inhibitor on mice were examined. Mice were randomly divided into four groups: CDDP, PARP inhibitor, combination, and control group. Cisplatin and the PARP inhibitor were administered by intraperitoneal injection. At 1 month, weight significantly decreased in the CDDP and combination groups but recovered by months 3 and 6. Survival analysis indicated a significant decrease in the CDDP group by day 40. Regarding the gastrointestinal mucosa, no significant differences were observed between the control and PARP inhibitor groups. The CDDP group showed significant shortening of villi compared to the control and PARP inhibitor groups. The combination group did not exhibit significant villi shortening compared to the CDDP group and showed no significant difference from the control group. These findings suggest that the PARP inhibitor may mitigate the intestinal damage caused by cisplatin.

Free Research Field

口腔外科学

Academic Significance and Societal Importance of the Research Achievements

本研究において、PARP阻害剤を併用することによって、以前から報告されているCDDPの抗腫瘍効果の増強効果だけでなく、CDDPによる副作用軽減の両方を期待できることが示唆される結果が得られた。従って、さらに分子生物学的なメカニズム解明のための研究意義が生じるだけでなく、消化管症状を誘発させる他の抗腫瘍薬においても同様の検証を行う学術的意義が発生する。それにより抗腫瘍薬誘発消化管粘膜障害ならびに粘膜免疫応答の破綻によって発症する疾患のメカニズム解明につながる可能性が期待でき、当該疾患発症の予防法や治療法の新たな展開につながる社会的意義がある。