| Project/Area Number |
16K09347
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | Niigata University |
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Principal Investigator |
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| 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)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2017: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2016: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
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| Keywords | 肝がん / エクソソーム / 薬剤耐性 / シスプラチン / 消化器内科 / 肝臓学 |
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| 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.
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| 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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