Oncogenesis after hepatic arterial embolization

2018 Fiscal Year Final Research Report

• Project/Area Number: 17K16441
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Radiation science
• Research Institution: Kobe University
• Principal Investigator: Ueshima Eisuke 神戸大学, 医学部附属病院, 特定助教 (40645561)
• Research Collaborator: Takaki Haruyuki ; Kodama Hiroshi ; Nishiofuku Hideyuki ; Hirata Yutaka
• Project Period (FY): 2017-04-01 – 2019-03-31
• Keywords: TGF-β1 / HIF-1α

Outline of Final Research Achievements

Rats bearing N1S1 hepatoma cells underwent HAE. Animals were euthanized at 48h, and liver tissues were harvested. IHC and qPCR were performed to compare the expression of TGF-β1. In vitro experiments with the N1S1 cell line were performed under hypoxic conditions for 48h, and the expression of TGF-β1 and HIF-1α was assessed with western blotting and ELISA. IHC showed that both the TGF-β1 and HIF-1α-positive areas were larger in the HAE group than in the sham group. Similarly, qPCR showed that the mRNA expression levels of TGF-β1 and HIF-1α were higher in the HAE group than those in the sham group. TGF-β1 expression was suppressed when HIF-1α inhibitors were added, and HIF-1α expression was upregulated when exogenous TGF-β1 was added in N1S1 cells.

Free Research Field

Interventional Oncology

Academic Significance and Societal Importance of the Research Achievements

肝動脈塞栓術後の癌微小環境において、TGF-β1および HIF-1αが有意に発言していることが分かった。これらは低酸素により発現が促されており、お互い共依存的に上昇することが示された。現在、TGF-β1および HIF-1αの上昇から肝癌の再発・転移に繋がる複数の経路が判明している。これらの一部あるいは複数箇所に作用する阻害薬や抗体を用いることで、肝動脈塞栓術後の再発・転移を抑制し、予後の延長に寄与する可能性があることが示唆された、