2022 Fiscal Year Final Research Report
Role of inorganic polyphosphate on regulation of radio-sensitivity by modulating mitochondrial activity
Project/Area Number |
20K07987
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 52040:Radiological sciences-related
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Research Institution | Hokkaido University |
Principal Investigator |
Tsutsumi Kaori 北海道大学, 保健科学研究院, 助教 (80344505)
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Project Period (FY) |
2020-04-01 – 2023-03-31
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Keywords | ポリリン酸 / 放射線感受性 / ミトコンドリア / アデノシン三リン酸 |
Outline of Final Research Achievements |
The aim of this study was to elucidate the mechanism of radio-sensitization of the human lung non-small cell lung cancer cell line (H1299) by inorganic polyphosphate (polyP). The mitochondrial membrane potential was decreased by polyP reatment in a pyruvate-dependent manner, while the intracellular ATP levels were decreased in a pyruvate-independent manner. The amount of lactate secretion and the glucose-6-phosphate dehydrogenase activity were not different respectively between the polyP-treated and control groups, and there was no association with the glycolytic system or pentose phosphate circuit. The polyP-induced decrease in intracellular ATP was also observed in the presence of cyclosporine A, an inhibitor of mitochondrial membrane permeability transition pore (mPTP) activity, suggesting that the polyPe-induced decrease in ATP was caused by a pathway other than mPTP activity.
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Free Research Field |
放射線科学
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Academic Significance and Societal Importance of the Research Achievements |
これまで、ポリリン酸による腫瘍の放射線感受性増感効果や細胞内ATP量の低下を確認していたが、その作用機序については不明であった。本研究によって、ミトコンドリア膜透過性遷移孔(mPTP)活性への関与や解糖系、ペントースリン酸回路への関連性がみられなかったことから、これらの経路以外にポリリン酸が作用している可能性が明らかとなった。ポリリン酸は放射線感受性を高めるだけでなく、腫瘍の転移抑制効果を併せ持つことが報告されている。また、生体内高分子であるため生体への安全性は高い。今後の更なるメカニズムの解明により、ポリリン酸利用した効果的な放射線治療薬研究の発展が期待される。
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