| Project/Area Number |
17K17237
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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 |
Surgical dentistry
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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 |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | アデノシン受容体 / ADORA2B / 口腔癌 / HIF-1α / Theophylline / アデノシン / ADORA2b / 口腔扁平上皮癌 / HIF1α / HIF1-α |
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| Outline of Final Research Achievements |
Adenosine A2b receptor (ADORA2B) is up-regulated in the OSCC derived cell lines and clinical samples and it is cleared that ADORA2B strongly effects the tumoral growth by the analyses of the correlation with the clinical indicator and functional analyses used shRNA transfection models. ADORA2B promotes the OSCC progression by regulating the HIF-1α target genes via AKT/ERK-HIF1α signaling pathway started from ADORA2B. We identified the Theophylline is the ADORA2B directly inhibitor, inhibits ADORA2B signaling cascade, as a results, Theophylline depressed OSCC development by controlling hypoxia metabolism and cell death. This study may contribute to the future clinical applications.
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| Academic Significance and Societal Importance of the Research Achievements |
アデノシンA2b受容体 (ADORA2B)はAKT/ERK-HIF-1α経路を介して、HIF-1α標的遺伝子群を調整することで口腔癌の進展調節を行うと考えられた。ADORA2Bの阻害薬として同定したTheophyllineはADORA2Bを起点とするカスケード抑制による、癌細胞の嫌気性代謝の抑制、細胞死への誘導により口腔癌の進展を制御する可能性が示唆された。以上よりADORA2Bは口腔扁平上皮癌の新たなバイオマーカーとなりうると考えられた。また、ADORA2B阻害薬として同定したTheophyllineは新たな分子標的治療薬となりうる可能性が示唆された。
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