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

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K08308
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pharmacology in pharmacy
• Research Institution: The University of Tokushima
• Principal Investigator: FUJINO Hiromichi 徳島大学, 大学院医歯薬学研究部(薬学域), 教授 (40401004)
• Project Period (FY): 2017-04-01 – 2020-03-31
• 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

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.

Free Research Field

分子細胞薬理学

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。