徳島大学 教育・研究者情報データベース(EDB)

1. (英) Wada Hironori / (日) 和田 浩典 / (読) わだ ひろのり

   役割	任意
   貢献度	任意
   学籍番号	推奨	****

2. 佐藤 康史([徳島大学.大学院医歯薬学研究部.医学域.連携研究部門(医学域).寄附講座系(医学域).地域消化器・総合内科学])

   役割	任意
   貢献度	任意
   学籍番号	推奨

3. (英) Fujimoto Shota / (日) 藤本 将太 / (読) ふじもと しょうた

   役割	任意
   貢献度	任意
   学籍番号	推奨	****

4. 岡本 耕一([徳島大学.病院.診療科.内科.消化器内科])

   役割	任意
   貢献度	任意
   学籍番号	推奨

5. 板東 正浩([徳島大学.大学院医歯薬学研究部.医学域.医科学部門.内科系.消化器内科学])

   役割	任意
   貢献度	任意
   学籍番号	推奨

6. 川口 智之([徳島大学.病院.診療科.内科.消化器内科])

   役割	任意
   貢献度	任意
   学籍番号	推奨

7. 宮本 弘志([徳島大学.大学院医歯薬学研究部.医学域.医科学部門.内科系.消化器内科学]/[徳島大学.病院.診療科.内科.消化器内科])

   役割	任意
   貢献度	任意
   学籍番号	推奨

8. 六車 直樹

   役割	任意
   貢献度	任意
   学籍番号	推奨

9. (英) Horimoto Katsuhisa

   役割	任意
   貢献度	任意
   学籍番号	推奨

10. (英) Matsuzawa Yui

    役割	任意
    貢献度	任意
    学籍番号	推奨

11. (英) Mutoh Michihiro

    役割	任意
    貢献度	任意
    学籍番号	推奨

12. 高山 哲治([徳島大学.大学院医歯薬学研究部.医学域.医科学部門.内科系.消化器内科学])

    役割	任意
    貢献度	任意
    学籍番号	推奨

(英) Resveratrol inhibits development of colorectal adenoma via suppression of LEF1; comprehensive analysis with connectivity map.

(英) Although many chemopreventive studies on colorectal tumors have been reported, no effective and safe preventive agent is currently available. We searched for candidate preventive compounds against colorectal tumor comprehensively from United States Food and Drug Administration (FDA)-approved compounds by using connectivity map (CMAP) analysis coupled with in vitro screening with colorectal adenoma (CRA) patient-derived organoids (PDOs). We generated CRA-specific gene signatures based on the DNA microarray analysis of CRA and normal epithelial specimens, applied them to CMAP analysis with 1309 FDA-approved compounds, and identified 121 candidate compounds that should cancel the gene signatures. We narrowed them down to 15 compounds, and evaluated their inhibitory effects on the growth of CRA-PDOs in vitro. We finally identified resveratrol, one of the polyphenolic phytochemicals, as a compound showing the strongest inhibitory effect on the growth of CRA-PDOs compared with normal epithelial PDOs. When resveratrol was administered to Apc mice at 15 or 30 mg/kg, the number of polyps (adenomas) was significantly reduced in both groups compared with control mice. Similarly, the number of polyps (adenomas) was significantly reduced in azoxymethane-injected rats treated with 10 or 100 mg/resveratrol compared with control rats. Microarray analysis of adenomas from resveratrol-treated rats revealed the highest change (downregulation) in expression of LEF1, a key molecule in the Wnt signaling pathway. Treatment with resveratrol significantly downregulated the Wnt-target gene (MYC) in CRA-PDOs. Our data demonstrated that resveratrol can be the most effective compound for chemoprevention of colorectal tumors, the efficacy of which is mediated through suppression of LEF1 expression in the Wnt signaling pathway.

1. (英) Mice
2. (英) Rats
3. (英) Animals
4. (英) Resveratrol
5. (英) Adenoma
6. (英) Colorectal Neoplasms
7. (英) Wnt Signaling Pathway
8. (英) Chemoprevention
9. (英) Lymphoid Enhancer-Binding Factor 1

1. (英) Article.ELocationID: 10.1111/cas.15576

2. (英) Article.PublicationTypeList.PublicationType: Journal Article

3. (英) KeywordList.Keyword: LEF1

4. (英) KeywordList.Keyword: chemoprevention

5. (英) KeywordList.Keyword: colorectal adenoma

6. (英) KeywordList.Keyword: connectivity map

7. (英) KeywordList.Keyword: resveratrol