| Project/Area Number |
17K17266
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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 | Saga University |
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Principal Investigator |
Aijima Reona 佐賀大学, 医学部, 助教 (30756143)
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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: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | TRPチャネル / 口腔癌 / 温度感受性 |
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| Outline of Final Research Achievements |
Transient receptor potential (TRP) channels are a family of Ca2+-permeable nonselective cation channels. In this study, we investigated regulation mechanisms and clinical application of TRP channels in oral squamous cell carcinoma. We found more TRPV4 expression in HSC4 than in HSC2 and HSC3. We observed that a selective TRPV4 agonist significantly and continuously increased intracellular Ca2+ concentration in HSC4. TRPV4 agonist-induced increase in intracellular Ca2+ concentrations in HSC4-siTRPV4, HSC2, and HSC3 were lower than that in HSC4-siCTRL. In addition, TRPV4 stimulation-induced phosphorylation of Jun N-terminal kinase and p38, and cell death were also inhibited in HSC4-siTRPV4. Furthermore, knockdown of TRPV4 in HSC4 reduced adherens junction molecules and enhanced cell migration. These results suggest that regulation of TRPV4 channels would be a novel therapeutic approach for oral cancer.
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| Academic Significance and Societal Importance of the Research Achievements |
口腔癌におけるTRPチャネルを標的とした基礎的研究はこれまでに報告がなかった。本研究により口腔癌に発現するTRPチャネルの機能調節が癌細胞の性質を変化させ、治療応用も可能であることが示唆された。また、既存の抗癌剤を減量させる可能性も明らかにでき、副作用低減や完遂率の改善にも繋がる新しい多剤併用療法の可能性を秘めている。イオンチャネル製剤は低分子化合物であることから、比較的安価で大量生産が可能である。このことは、がん患者増加による医療費高騰に対しても、医療費抑制という社会的課題を解決する一つの方法にもなりうると考える。
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