Effects of Scutellarin on Antiangiogenesis of Pancreatic Cancer through Suppression of Girdin for Clinical Application

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K18098
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55020:Digestive surgery-related
• Research Institution: Nagoya City University
• Principal Investigator: Maeda Anri 名古屋市立大学, 医薬学総合研究院(医学), 研究員 (70825471)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: 膵癌 / Girdin / スクテラリン / 遊走能 / 血管新生能 / VEGF-A / pGirdin（Tyr-1746）

Outline of Final Research Achievements

In this study, we focused on the functional analysis of Girdin in pancreatic cancer. (1) In clinical pancreatic cancer specimens, high Girdin expression in pancreatic cancer patients was associated with significantly poorer prognosis (OS and RFS). We also found a significant correlation between Girdin expression and T factors of TNM classification. (2) In vitro experiments using pancreatic cancer cell lines showed that Girdin expression was high in many pancreatic cancer cell lines, and knockdown of Girdin significantly suppressed EGF-stimulated migration and VEGF-A-mediated angiogenesis. We confirmed that scutellarin inhibits Girdin phosphorylation and suppresses EGF-stimulated migration.

Free Research Field

消化器外科

Academic Significance and Societal Importance of the Research Achievements

Girdinは細胞運動に関与するタンパクとして本邦で発見されたが，一部の癌腫では腫瘍増殖能や遊走・浸潤能，血管新生能に関与することが報告されている．本研究では，予後の不良な膵癌におけるGirdinの機能解析を通して，Girdinが新たな予後マーカーになりうる可能性が示唆された．また，Girdinが膵癌遊走能および血管新生に関与することが考えられ，Girdinの抑制が新たな治療薬となりうることが検証された．そのうち，フラボノイドのスクテラリンは，Girdin阻害を通じて腫瘍遊走能を抑制しうる可能性が示唆された．これらの結果が今後の臨床応用につながり，膵癌予後の改善に寄与することが期待された．