Escin inhibits angiogenesis by blocking nuclear factor-kB activation in pancreatic cancer cell lines

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K18157
• 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: Omi Kan 名古屋市立大学, 医薬学総合研究院(医学), 研究員 (60825488)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: 膵癌 / 血管新生 / NF-ｋB / VEGF / IL-8 / anigiogenesis

Outline of Final Research Achievements

Escin, from the horse chestnut, has been reported to suppress the NF-κB in several cancers. Our previous study showed that NF-κB enhanced angiogenesis in PaCa. We examined whether escin inhibited angiogenesis by blocking NF-κB activation in PaCa. Escin, in concentration of over 10 μM, inhibited the proliferation of several PaCa cell lines. In immunocytochemical staining, escin inhibited the nuclear translocation of NF-κB. NF-κB ELISA showed that NF-κB activity in escin-treated PaCa cells was inhibited and RT-PCR showed that the mRNA expression levels of IL-8 and VEGF were suppressed following escin treatment in the PaCa cell lines. ELISA showed escin decreased the production of IL-8 and VEGF. Tube formation in immortalized human endothelial cells was inhibited following incubation with the supernatants from escin-treated PaCa cells. These results indicated that escin inhibited angiogenesis by reducing the production of IL-8 and VEGF via blocking NF-κB activity in PaCa.

Free Research Field

膵癌

Academic Significance and Societal Importance of the Research Achievements

膵癌は悪性度が極めて高く、より効果のある新規治療薬の開発は急務である。我々は今までに、膵癌の転移や血管新生に転写因子NF-κBが重要な役割を果たしていることを報告してきた。転移能の高い膵癌は恒常的にNF-κB の活性が高く、その下流のVEGFやIL-8といった血管新生因子の産生能を亢進し悪性度を高めている。以上より、NF-κBは新規分子標的薬のターゲットになりうるが、既存のNF-κB阻害薬は副作用が強く長期投与が困難で、膵癌では臨床応用に至っていない。今回、天然化合物エスシンが膵癌の血管新生能を低下させることが示唆されたため、動物実験等を今後行い、臨床応用につなげられる可能性がある。