| Project/Area Number |
17K10594
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Digestive surgery
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| Research Institution | Saga University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
北島 吉彦 佐賀大学, 医学部, 客員研究員 (30234256)
田中 智和 佐賀大学, 医学部, 助教 (60781903)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | HIF-1α / 活性酸素 / 脂肪酸合成 / 低酸素環境 / YC-1 / パルミチン酸 / カルニチン / 癌 / Warburg効果 / 脂肪酸代謝 |
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| Outline of Final Research Achievements |
HIF-1α knockdown (KD) and control (Sc) cells were prepared using two types of gastric cancer cell lines (As9 and MKN74) by transfected technique. Antitumor effect by HIF-1α inhibition under hypoxic environment was confirmed. Moreover, additional of palmitic acid (PA) and carnitine enhanced antitumor effect. The HIF-1α inhibitor, YC-1 also showed similar results to the HIF-1α KD cells even when adding PA and carnitine. At that time, reactive oxygen species (ROS) increased in HIF-1α KD cells and cells treated by YC-1, and PA and carnitine tended to enhance ROS production. From our results of the in vitro experiments, HIF-1α is a central factor in the inhibition of fatty acid β oxidation and ROS regulation, and inhibition of HIF-1α and addition of fatty acid and low molecular weight carnitine induce hypoxia-induced apoptosis.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究は低酸素環境下における癌の脂肪酸代謝に着目した独創的な胃癌薬物療法の確立を目指すものである。依然として仮説検証の実験中ではあるが、これまでの結果より、HIF-1αを阻害に加えて脂肪酸代謝を促進するパルミチン酸およびカルニチンを投与することによって抗腫瘍効果が増強されることを確認しており、今後の仮説検証に期待の持てるものとなっている。手術不能胃癌患者は経口接種困難な場合が多く、長期低栄養状態は癌悪液質を来し生命予後を悪化させる。将来的には、経静脈的に脂肪乳剤（脂肪酸含有）およびHIF-1α阻害薬+カルニチン併用療法が栄養改善と抗腫瘍効果を併せ持つ画期的胃癌治療薬となることが期待される。
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