Development of preventive nucleic acid drugs against lung metastasis of osteosarcoma

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K10861
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: Tottori University
• Principal Investigator: Osaki Mitsuhiko 鳥取大学, 医学部, 准教授 (40325006)
• Research Collaborator: OKADA futoshi ; HIRAHATA mio ; TSUGE minori ; SASAKI ryo ; IZAWA hironori
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: miR-143 / イヌ骨肉腫 / 肺転移

Outline of Final Research Achievements

Previously, we revealed that intravenous injection of miR-143 suppressed lung metastasis of human osteosarcoma cells in a mouse model. In this study, we examined whether the invasion and metastasis of canine osteosarcoma cells could be suppressed by miR-143 injection which would serve as a basis for a future preclinical study using dogs. Transfection of miR-143 inhibited cell invasion and injection of miR-143 suppressed lung metastasis of canine osteosarcoma cells in a mouse model. A carrier is needed to safely and efficiently introduce miR-143 into tumor cells. Although some peptides or chitosan were used as carriers, their solubility and efficiency for transfecting miR-143 into tumor cells were not sufficient.

Free Research Field

腫瘍病理学

Academic Significance and Societal Importance of the Research Achievements

本研究は、新規医薬品として注目されて開発が進められている「核酸医薬」によって、骨肉腫の予後を規定する肺転移を予防する方法の構築を目指している。合成miR-143を肺転移予防の核酸医薬として臨床応用するための前臨床試験として、ヒト骨肉腫の病態と類似性の高いイヌを用いた安全性および肺転移予防効果の検証が非常に有用である。本研究成果は、ヒト骨肉腫細胞のみならずイヌ骨肉腫細胞に対するmiR-143の肺転移予防効果を実証し、骨肉腫罹患犬を対象とした前臨床試験の成果がヒトへの効果を予測するモデルとなることを強く示唆することができた。