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2018 Fiscal Year Final Research Report

The mechanism of exosome-mediated drug resistance in hepatoma cells

Research Project

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Project/Area Number 16K09347
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Gastroenterology
Research InstitutionNiigata University

Principal Investigator

Yasunobu MATSUDA  新潟大学, 医歯学系, 准教授 (40334669)

Co-Investigator(Kenkyū-buntansha) 山際 訓  新潟大学, 医歯学総合研究科, 特任教授 (10419327)
永橋 昌幸  新潟大学, 医歯学総合病院, 研究准教授 (30743918)
小林 隆  新潟大学, 医歯学総合病院, 講師 (40464010)
若井 俊文  新潟大学, 医歯学系, 教授 (50372470)
Project Period (FY) 2016-04-01 – 2019-03-31
Keywords肝がん / エクソソーム / 薬剤耐性
Outline of Final Research Achievements

Recently, it has been regarded that cells secret exosome (nano-sized vesicles (20-100 nm)), which participate in various types of cell-cell communication. In this study, we examined the mechanism of exosome secretion in hepatoma cells, and found that exosome exert drug resistance to anticancer drugs. Our obtained results showed that anticancer drugs (cisplatin and 5-fluorouracil) stimulate the secretion of exosome in human hepatoma cells. When cells were incubated with anticancer drug-treated cells-derived exosome, they acquired strong resistance to anticancer drugs. We found that activated type of mTOR, a serine-threonine kinase which plays a pivotal role in the cell survival, was significantly increased in exosome. Collectively, exosome exerts drug resistance through mTOR signaling in hepatoma cells.

Free Research Field

消化器内科

Academic Significance and Societal Importance of the Research Achievements

肝がんは、抗がん剤に耐性を有する悪性疾患である。本研究では、細胞から分泌される微小粒子の一種であるエクソソームに着目し、薬剤耐性との関連性を検討した。研究の結果、かんがんにおいては、細胞生存に重要なキナーゼ蛋白を多く含むエクソソームを分泌することによって抗がん剤に対する耐性を獲得していることが明らかになった。本研究により、エクソソームに着目したがん治療の有効性が示唆された。

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Published: 2020-03-30  

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