Establishment a new 5-FU therapy in pancreatic cancer through the combination of tumor-specific DPD expression inhibitory compounds

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K16225
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 49030:Experimental pathology-related
• Research Institution: Nagoya City University
• Principal Investigator: Hiroyuki Kato 名古屋市立大学, 医薬学総合研究院(医学), 講師 (80791293)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 膵癌 / 5-FU / DPYD / ルテオリン

Outline of Final Research Achievements

It was found that Luteolin, a type of flavonoid, has a suppressive effect on pancreatic cancer development and inhibits the expression of DPYD, a 5-FU degradation enzyme. Therefore, this study examined the pancreatic cancer suppression effect of combined administration of Luteolin and 5-FU. Using KPPC mice models and xenograft models of human pancreatic cancer cell lines with DPYD overexpressed, it was revealed that combined administration showed a significant tumor suppression effect. Additionally, it was found that DPYD contributes to proliferation, invasion, and angiogenesis, and that metallopeptidase activity including MMP9 and MEP1A contributes to invasion. Results of examining substances with flavonoids other than Luteolin or with modified side chains showed that Luteolin has the highest inhibitory effect on DPYD. This study suggests the potential for pancreatic cancer suppression through combined administration of Luteolin and 5-FU.

Free Research Field

実験病理

Academic Significance and Societal Importance of the Research Achievements

ルテオリンはサプリメントとしても販売されている安全性の高い物質である。現在までにフラボノイドなどの生理活性物質は単独での薬効はそれほど高くないため、化学予防物質などでの研究がなされてきた。本研究は5-FUという膵癌の標準治療と組み合わせることによって、5-FUの治療特異的に治療効果を上昇する事が期待でき、予後の悪い膵癌への治療応用性が期待できる有用な物質である可能性がある。安全性も担保された臨床応用可能な物質であり、その社会的意義や還元性は高いと考えられる。