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2020 Fiscal Year Final Research Report

Treatment strategy of ovariam cancer, targeting the new programed all dezth, "Ferroptosis".

Research Project

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Project/Area Number 18K09257
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 InstitutionGifu University

Principal Investigator

Morishige Ken-ichirou  岐阜大学, 大学院医学系研究科, 教授 (90283788)

Co-Investigator(Kenkyū-buntansha) 竹中 基記  岐阜大学, 医学部附属病院, 助教 (20566484)
上田 陽子  岐阜大学, 医学部附属病院, 医員 (20795075)
鈴木 紀子  岐阜大学, 大学院医学系研究科, 助教 (40642096)
森 美奈子  岐阜大学, 医学部附属病院, 助教 (60585610)
Project Period (FY) 2018-04-01 – 2021-03-31
Keywords卵巣癌 / フェントン反応 / フェロトーシス / オートファジー / フェリチン
Outline of Final Research Achievements

The mechanism of action of elastin, an inducer of ferrotosis, is to inhibit the function of the cystine transporter, thereby suppressing cystine uptake into the cell, leading to a decrease in intracellular glutathione and consequently an increase in the amount of intracellular reactive oxygen species produced by the Fenton reaction from divalent iron, resulting in lipid oxidation and cell death. This is the mechanism that induces lipid oxidation and cell death. This effect was also observed with sulfasalazine.
On the other hand, artesunate did not affect the cystine transporter activity, but promoted ferritin-specific autophagy (ferritinophagy), which released ferritin-bound iron, increased intracellular divalent iron, and increased the amount of intracellular ROS produced by the Fenton reaction.

Free Research Field

産科婦人科学

Academic Significance and Societal Importance of the Research Achievements

卵巣がんでは粘液性癌、(低異型)漿液性癌、明細胞癌などの一部にRas変異が認められており、これらは抗がん剤抵抗性である。これらの化学療法抵抗性腫瘍に対して有用な抗がん剤を見つけ出すためにはがんの原因となるドライバー変異の解析だけでなく、異なるプログラム細胞死を誘導する抗がん剤の開発が重要となる。その点においてRas変異卵巣がんにおけるフェロトーシスの解析と誘導薬の研究は抗がん剤抵抗性の卵巣がん治療薬の開発につながりうるものである。

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Published: 2022-01-27  

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