| Project/Area Number |
17K16040
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Respiratory organ internal medicine
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| Research Institution | Chiba University |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Keywords | 悪性胸膜中皮腫 / ネクロプトーシス / 薬剤耐性 / 癌 |
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| Outline of Final Research Achievements |
We assessed the efficacy of introducing necroptotic cell death on malignant mesothelioma cells. The method of combination with TNF-α, IAP inhibitor and pan-caspase inhibitor showed the highest efficacy in introducing necroptosis. We confirmed the necroptosis by inhibition of cell death using necrostatin-1, increase the amount of phosphorylate proteins of RIPK1, RIPK3 and MLKL, and morphological change observed by the electron microscope. In cisplatin-resistant malignant mesothelioma cells, the cell deaths through necroptosis were observed more compared to in wild type or pemetrexed-resistant type. The expression level of MDR1, MRP1 and MRP2 that are related to cisplatin resistance did not show a correlation to the efficacy of necroptosis.
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| Academic Significance and Societal Importance of the Research Achievements |
悪性胸膜中皮腫はアスベスト曝露と密接に関連し，壁側胸膜の中皮細胞から発生する極めて予後不良の腫瘍である．今後わが国で増加すると予想されている悪性腫瘍のひとつである．しかしながら，悪性胸膜中皮腫に対する有効な治療法の確立は遅れており，新しい治療法が待たれている．悪性胸膜中皮腫に対するネクロプトーシス誘導の報告は少ない．今回我々が誘導に成功した方法を用い，ネクロプトーシス誘導を悪性胸膜中皮腫の治療として発展させるための基本的アプローチ方法として今後応用できる可能性がある．
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