Development of YB-1-silencing miRNA/ decoy gene therapy against intractable solid tumor to regulate malignant microcircumstances

2014 Fiscal Year Final Research Report

• Project/Area Number: 24390322
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Kyushu University
• Principal Investigator: NAKANO Kenji 九州大学, 先端融合医療レドックスナビ研究拠点, 教授 (00315061)
• Co-Investigator(Kenkyū-buntansha): KATANO Mitsuo 九州大学, 大学院医学研究院, 教授 (10145203) ; KATAOKA Kazunori 東京大学, 大学院工学研究科, 教授 (00130245)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: YB-1 / miRNA / デコイ / 癌微小環境 / 血管新生 / 遺伝子治療

Outline of Final Research Achievements

The purpose of this study is to develop YB-1 silencing miRNA/ decoy gene therapy against intractable solid tumors to regulate tumor angiogenesis. Block/homo-polyplex micelles, which encapsulate YB-1 miRNA/decoy expression plasmid with and without exportin-5 (Xpo-5) and argonaoute-2 (Ago-2) plasmids, were intraperitoneally administered in nude mice harboring disseminated pancreatic cancer. The disseminated tumors were inhibited in the YB-1 miRNA/decoy alone and the combination treatment groups compared with the controls, but there was no significant prolongation of survival between the treatment and control groups. The microvascular density was decreased in tumor tissues treated with miRNA/decoy compared with the controls. However, the localization of micelles was limitedlly detected in the peripheral area of tumor tissues. These results suggest that YB-1 silencing is promising strategy for antiangiogenesis treatment and more efficient transduction devices may resolve the issues.

Free Research Field

消化器外科