Effects of intravascular administration of acridine orange and bisphosphonate in a local bone metastasis of breast cancer model

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K09640
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56020:Orthopedics-related
• Research Institution: Akita University
• Principal Investigator: Tsuchie Hiroyuki 秋田大学, 医学部附属病院, 助教 (80513019)
• Co-Investigator(Kenkyū-buntansha): 永澤 博幸 秋田大学, 医学部附属病院, 助教 (50375284) ; 宮腰 尚久 秋田大学, 医学系研究科, 教授 (90302273)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 転移性骨腫瘍 / アクリジンオレンジ / ビスホスホネート

Outline of Final Research Achievements

This study evaluated the effect of hematogenous administration of acridine orange (AO) alone and in combination with zoledronate (ZOL) on bone metastases. E0771 cells were injected directly into the right femur of female mice. The mice were divided into five groups according to treatment and were reared and sacrificed after six weeks. At four weeks, the bone destruction rate was lower in the AO+ZOL group than in the radiation group. At six weeks, the AO+ZOL group had a lower bone destruction rate than the control and radiation groups; the ZOL group had a lower rate than the radiation group. The AO and AO+ZOL groups had suppressed tumor weight and volume compared to the control and radiation groups. The number of extraosseous apoptotic cells was higher in the AO+ZOL group than in all other groups except the AO group. In a model of local bone metastasis of breast cancer, hematogenous administration of AO reduced tumor size and more so when combined with ZOL.

Free Research Field

整形外科　がん治療

Academic Significance and Societal Importance of the Research Achievements

転移性骨腫瘍はADLを大きく低下させ、進行を予防するために骨吸収抑制剤を一般に用いるが、完全に進行を抑えることは難しい。AOはこれまで骨肉腫などに対する抗腫瘍効果が報告されていたが、がん患者に対する報告はほとんどされておらず、転移性骨腫瘍に対する効果もまた検討されていない。転移性骨腫瘍対する新規治療薬としてAOが有効である可能性、さらにはZOLとの併用効果を検討することで、がん患者のADL低下予防、進行予防となる可能性がある。