Characteristics of colorectal carcinogenesis based on metabolic syndrome: molecular abnormality and alteration of miRNA expression

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K15936
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Gastroenterology
• Research Institution: Gifu University
• Principal Investigator: Kubota Masaya 岐阜大学, 医学部附属病院, 助教 (90542407)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 肥満関連大腸発癌 / 大腸癌 / 化学予防

Outline of Final Research Achievements

This study was conducted focusing on environmental factors such as lifestyle-related diseases and gene abnormalities in colorectal carcinogenesis. A novel obesity-related colorectal carcinogenesis model was constructed by crossing APC-mutated Min mouse and db/db mouse exhibiting obesity/type 2 diabetes. It was found that this mouse developed obesity, hyperglycemia, hyperinsulinemia, and dyslipidemia, and that the incidence of tumors in the intestinal tract increased significantly compared to the control. Administration of the anti-diabetic drug metformin and green tea catechin to the mice reduced the number of intestinal tumors. Moreover, development of colorectal neoplasms was suppressed by an anti-diabetic drug SGLT2 inhibitor in a colon carcinogenesis model using db/db mice. The results indicated the possibility that obesity-related colorectal carcinogenesis is suppressed by anti-diabetic agents and phytochemicals.

Free Research Field

大腸癌基礎

Academic Significance and Societal Importance of the Research Achievements

肥満や糖尿病をはじめとする生活習慣病患者の増加は重要な社会問題であり、また、これらの疾患を合併する大腸癌患者の増加が危惧されている。本研究結果は、臨床で使用されている糖尿病治療薬や日常生活で摂取可能な植物由来化学物質（phytochemical）が、肥満に関連する大腸発癌を抑制する上で有効であることを示しており、大腸発癌リスクの高い肥満や糖尿病を合併した患者の予後改善・再発予防への寄与が期待できる。