Exploring the mechanism of EP4 prostanoid receptor-evoked colorectal cancer development during the collapse of homeostasis and its ameliorating effects by substances of type 2 innate immune system
| Project/Area Number |
17K08308
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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 |
Pharmacology in pharmacy
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| Research Institution | The University of Tokushima |
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Principal Investigator |
FUJINO Hiromichi 徳島大学, 大学院医歯薬学研究部(薬学域), 教授 (40401004)
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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 |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
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: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | プロスタノイド受容体 / EP4受容体 / 酪酸 / ヒスタミン / IL-4 / 大腸癌 / ２型免疫 / PGE2 / 結腸癌 / 薬理学 / 薬学 |
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| Outline of Final Research Achievements |
By using the human colon cancer HCA-7 cell line, we examined the effects of microbiota produced butyrate, as well as physiologically active substances in type 2 innate immune system, such as histamine and interleukin (IL)-4, on the colon cancer malignancy. As a result, they were found to inhibit prostaglandin E2-stimulated EP4 prostanoid receptor-mediated signal transduction pathways. Therefore, the possibility that butyrate, histamine as well as IL-4 are found to be able to inhibit the cancer malignancy signaling pathways of HCA-7 cells by reducing the expression of EP4 receptors, though different mechanisms. Thus, these results strongly suggest that homeostasis maintaining butyrate as well as the type 2 innate immune system maintaining bioactive substances such as histamine and IL-4, could ameliorate the colorectal cancer malignancy.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究は、短鎖脂肪酸を栄養学的側面からではなく本有的な生理活性物質としてとらえ、その癌制御作用の解析と共に、２型免疫を担う生理活性物質について、EP4受容体系への影響を中心に考究し、ホメオスタシス破綻時における大腸癌の発症そして改善の分子メカニズムを明らかにすべく取り組んだ。その結果、恒常性を維持するために必要な酪酸、そして２型免疫系細胞の産生するIL－4やヒスタミンなどの生理活性物質は、大腸癌に対して改善効果を有する可能性が強く示唆された。本研究により大腸癌発症機構の最初期を抑制できる可能性を示せたことで、これまでとは異なる新たな側面からの治療・予防薬の開発に繋げることができると考えている。
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Report
(4 results)
Research Products
(31 results)
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[Journal Article] Cellular density-dependent increases in HIF-1α compete with c-Myc to down-regulate human EP4 receptor promoter activity through Sp-1-binding region2018
Author(s)
Seira N, Yamagata K, Fukushima K, Araki Y, Kurata N, Yanagisawa N, Mashimo M, Nakamura H, Regan JW, Murayama T, Fujino H
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Journal Title
Pharmacol Res Perspect
Volume: 6
Issue: 6
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Hydrocortisone administration was associated with improved survival in Japanese patients with cardiac arrest.2017
Author(s)
48)Niimura T, Zamami Y, Koyama T, Izawa-Ishizawa Y, Miyake M, Koga T, Harada K, Ohshima A, Imai T, Kondo Y, Imanishi M, Takechi K, Fukushima K, Horinouchi Y, Ikeda Y, Fujino H, Tsuchiya K, Tamaki T, Hinotsu S, Kano MR, Ishizawa K.
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Journal Title
Scientific Reports
Volume: 7
Issue: 1
Pages: 17919-17919
DOI
NAID
Related Report
Peer Reviewed / Open Access
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[Presentation] HIF-1α and c-Myc oppositely regulate human EP4 receptor promoter activity in human colon cancer HCA-7 cells.2019
Author(s)
山形 一行, 清良 尚史, 福島 圭穣, 荒木 裕美, 倉田 直希, 柳澤 直樹, 間下 雅士, 中村 浩之, REGAN W. John, 村山 俊彦, 藤野 裕道．
Organizer
第92会日本薬理学会年会
Related Report
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[Presentation] Hypoxia inducible factor-1alpha regulates human EP4 receptor expression by binding to specificity protein-1.2018
Author(s)
Naofumi Seira, Kazuyuki Yamagata, Keijo Fukushima, Yumi Araki, Naoki Kurata, Naoki Yanagisawa, Masato Mashimo, Hiroyuki Nakamura, John W. Regan, Toshihiko Murayama, Hiromichi Fujino.
Organizer
The 3rd Chiba University-Mahidol University Joint Symposium on Pharmaceutical Sciences
Related Report
Int'l Joint Research / Invited
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[Presentation] Renoprotective effects of edoxaban, a factor Xa inhibitor．2018
Author(s)
Yuya Horinouchi, Yasumasa Ikeda, Keijo Fukushima, Masaki Imanishi, Yuki Izawa-Ishizawa, Yoshito Zamami, Hiromichi Fujino, Keisuke Ishizawa, Koichiro Tsuchiya, Toshiaki Tamaki.
Organizer
18th World Congress of Basic and Clinical Pharmacology,
Related Report
Int'l Joint Research
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[Presentation] Search for drugs that attenuate the anti tumor effect of bevacizumab using adverse event database.2018
Author(s)
Yoshito Zamami, Yuki Izawa-Ishizawa, Kenshi Takechi, Masaki Imanishi, Keijo Fukushima, Yuya Horinouchi, Yasumasa Ikeda, Hiromichi Fujino, Toshiaki Tamaki, Keisuke Ishizawa.
Organizer
18th World Congress of Basic and Clinical Pharmacology,
Related Report
Int'l Joint Research
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[Presentation] ヒト結腸がんHCA-7 細胞における酪酸によるEP4 受容体発現系への影響2018
Author(s)
渡嘉敷 夏海, 倉田 直希, 三竿 顕也, 荒木 祐美, 清良 尚史, 山際 菜月, 杉山 学, 福島 圭穣, REGAN John W, 村山 俊彦, 藤野 裕道
Organizer
日本薬学会第138年会
Related Report
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[Presentation] ドラッグリポジショニング手法を用いた心肺蘇生後脳症治療薬の探索2018
Author(s)
新村 貴博, 座間味 義人, 石澤 有紀, 今西 正樹, 武智 研志, 福島 圭穣, 堀ノ内 裕也, 池田 康将, 藤野 裕道, 土屋 浩一郎, 玉置 俊晃, 石澤 啓介
Organizer
日本薬学会第138年会
Related Report
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