| Project/Area Number |
18H02694
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Review Section |
Basic Section 50020:Tumor diagnostics and therapeutics-related
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| Research Institution | Kumamoto University |
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Principal Investigator |
BABA Hideo 熊本大学, 大学院生命科学研究部(医), 教授 (20240905)
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| Co-Investigator(Kenkyū-buntansha) |
美馬 浩介 熊本大学, 病院, 特任助教 (00546559)
石本 崇胤 熊本大学, 病院, 特任准教授 (00594889)
馬場 祥史 熊本大学, 病院, 特任准教授 (20599708)
今村 裕 公益財団法人がん研究会, 有明病院 消化器外科, 医長 (70583045)
原田 和人 熊本大学, 病院, 特任助教 (70608869)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2020: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2019: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2018: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
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| Keywords | 腸内細菌 / 食道癌 / 抗癌剤 / Fusobacterium nucleatum / 腸内細菌叢 / Microbiome / 化学療法 / 抗がん剤 / Fusobacterium / 抗癌剤感受性 / autophagy |
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| Outline of Final Research Achievements |
Fusobacterium nucleatum (F. nucleatum) is a gut microbe implicated in gastrointestinal tumorigenesis. The present study investigate the relationship between F. nucleatum and chemotherapeutic resistance in esophageal squamous cell carcinoma (ESCC). ESCC patients with F. nucleatum infection displayed lesser chemotherapeutic response. The infiltration and subsistence of F. nucleatum in the ESCC cells were observed by transmission electron microscopy and laser scanning confocal microscopy. We also observed that F. nucleatum modulates the endogenous LC3 and ATG7 expression, as well as autophagosome formation to induce chemoresistance against 5-FU, CDDP, and Docetaxel. ATG7 knock down resulted in reversal of F. nucleatum-induced chemoresistance. F. nucleatum confers chemoresistance to ESCC cells by modulating autophagy.
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| Academic Significance and Societal Importance of the Research Achievements |
腸内細菌叢はプロバイオティクス（Probiotics；人体に有益な腸内細菌叢ならびにこれらを含む食品・製品）やプレバイオティクス（Prebiotics；腸内細菌叢のバランスを改善する作用がある物質）により後天的に変化させることができる。今後の研究において、消化器癌進展におけるFusobacterium nucleatumの役割がより詳細に解明されれば、がん治療の新たな創薬に繋がる可能性があると考えている。
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