Effect of AdipoRon on the growth of pancreatic cancer cells in primary culture and obese prediabetic mice.

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K10594
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Chiba Cancer Center (Research Institute) (2018); Shimane University (2016-2017)
• Principal Investigator: Takenaga Keizo 千葉県がんセンター(研究所), がん遺伝創薬研究室, 特任研究員 (80260256)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: AdipoRon / 膵癌 / 糖尿病 / 肥満 / 腫瘍増殖

Outline of Final Research Achievements

Based on the finding that the antidiabetic drug AdipoRon induced cell death of human pancreatic cancer cells and reduced tumor growth in vivo, we examined the effect of AdipoRon on cell death in primary spheroid culture of pancreatic cancer cells isolated from pancreatic cancer patients. We found that AdipoRon induced necrotic cell death of pancreatic cancer cells in successfully established primary spheroid culture. We also examined the effect of AdipoRon on tumor growth of orthotopically implanted mouse pancreatic cancer cells in high-fat diet-induced obese prediabetic mouse model (B6J-DIO). We found that amelioration of obese rather than that of diabetic condition was important for suppression of tumor growth as well as the antitumor effect of AdipoRon.

Free Research Field

腫瘍生物学

Academic Significance and Societal Importance of the Research Achievements

アディポネクチン受容体に結合し抗糖尿病作用を示す薬剤として見出されたAdipoRonが膵癌患者由来の初代スフェロイド培養系において殺細胞効果を示すことが確認され、将来の治療に資する可能性がある。また、前糖尿病および肥満が膵癌の増殖、進展に影響するかどうかを、またそれに対してAdipoRon投与がどのような効果を示すかを肥満前糖尿病モデルマウスで検証し、糖尿病症状の軽減そのものよりも肥満の解消の方が膵癌増殖の抑制やAdipoRonの抗腫瘍効果に重要であることを見出した。