2023 Fiscal Year Final Research Report
Development of minimally invasive therapy focusing on the molecular mechanism of hypoxia in human papilloma virus-related head and neck cancer
| Project/Area Number |
21K16859
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 56050:Otorhinolaryngology-related
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| Research Institution | University of the Ryukyus |
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Principal Investigator |
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| Project Period (FY) |
2021-04-01 – 2024-03-31
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| Keywords | HIF-1a / HPV関連頭頸部癌 / HPV陽性細胞株 / HPV陰性細胞株 / mTOR阻害剤 |
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| Outline of Final Research Achievements |
The ultimate goal of this study is to elucidate the molecular mechanism of HPV-associated head and neck cancer under hypoxic conditions and to develop a novel therapeutic approach based on this mechanism.
HIF-1a expression was confirmed by Western blotting in HPV-positive and HPV-negative cell lines, and HIF-1a expression was observed in both lines under hypoxic conditions, but there was no significant difference. Preliminary experiments with mTOR inhibitors were completed, although not under hypoxic conditions, and the WST-1assay using a combination of four mTOR inhibitors suggested that phosphorylation of HIF-1a-related proteins (AKT, S6K, 4E-BP) was suppressed, which may have inhibited cell proliferation. This may have inhibited cell proliferation.
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| Free Research Field |
耳鼻咽喉科学関連
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| Academic Significance and Societal Importance of the Research Achievements |
低酸素状態下においてHPV陽性細胞株とHPV陰性細胞株においてもHIF-1aの発現を認めてはいるが有意差は認めなかった。よって酸素濃度変化（1％、21％）させてHIF-1aをノックダウンした場合の細胞増殖の程度と関連するタンパク質の発現を確認する必要がある。
またmTOR阻害剤によりHIF-1αの上流にある低酸素に関連する標的分子の抑制による細胞増殖抑制を見いだせたことにより、低酸素環境の状態でのHIF-1a関連タンパクや細胞増殖の評価をさらに検討することで将来的に低侵襲治療につなげていけるのではないかと考えている。
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