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2023 Fiscal Year Final Research Report

Establishment of a novel therapeutic strategy for drug-resistant ovarian cancer focusing on the glutathione synthesis pathway

Research Project

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Project/Area Number 21K09440
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 56040:Obstetrics and gynecology-related
Research InstitutionYamagata University

Principal Investigator

Seino Manabu  山形大学, 医学部, 講師 (40594320)

Co-Investigator(Kenkyū-buntansha) 永瀬 智  山形大学, 医学部, 教授 (00292326)
太田 剛  山形大学, 医学部, 准教授 (50375341)
Project Period (FY) 2021-04-01 – 2024-03-31
Keywords卵巣癌 / 明細胞癌 / グルタチオン / 化学療法抵抗性 / パクリタキセル
Outline of Final Research Achievements

This study demon-strated that combined treatment of paclitaxel (PTX) and the xCT inhibitor sulfasalazine (SAS) significantly enhanced cytotoxicity more than that by the individual drugs in OCCC cells. Treatment with PTX and SAS induced apoptosis more effectively than did individual drug treatments in the cells with significant generation of ROS. Moreover, Combined treatment of PTX and SAS induced ferroptosis in the cells with low expression of glutathione peroxidase (GPx4), high levels of intracellular iron and significant lipid ROS accumulation. Therefore, our findings provide valuable information that xCT inhibitor might be a promising therapeutic target for drug-resistant OCCC. The strategy of combined administration of PTX and SAS can potentially be used to treat OCCC and help to develop novel therapeutic methods.

Free Research Field

婦人科悪性腫瘍

Academic Significance and Societal Importance of the Research Achievements

卵巣癌は進行期で見つかることが多く予後不良な疾患である。卵巣癌で最も多い組織型は漿液性癌であり、比較的化学療法の効果が得られることが多い。一方卵巣明細胞癌は化学療法抵抗性であり、欧米人と比較すると日本人で多くみられる組織型である。本研究では卵巣明細胞癌に対してパクリタキセルとグルタチオン阻害薬であるスルファサラジンの併用が有効であることを証明した。このことにより予後不良である卵巣明細胞癌の化学療法抵抗性を克服し、予後改善に寄与できると考えられる。

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Published: 2025-01-30  

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