Intravascular Administration of Acridine Orange and Zoledronate in a Bone Metastasis Model of Breast Cancer

Anticancer Res. 2022 Nov;42(11):5357-5363. doi: 10.21873/anticanres.16041.

Abstract

Background/aim: This study evaluated the effect of haematogenous administration of acridine orange (AO) alone and in combination with zoledronate (ZOL) on bone metastases.

Materials and methods: E0771 cells (1.0×105 cells/10 μl) were injected directly into the right femur of female mice. The mice were divided into five groups according to treatment (drugs and irradiation) and were reared and sacrificed after 6 weeks. Micro-computed tomography (μCT) was performed to calculate the destruction rate of the femur bone. We measured tumour weight and volume at sacrifice and performed terminal deoxynucleotidyl transferase dUTP Nick-End Labelling staining of tumours.

Results: At 4 weeks, the bone destruction rate was lower in the AO+ZOL group than in the radiation group. At 6 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 tumour 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.

Conclusion: In a model of local bone metastasis of breast cancer, haematogenous administration of AO reduced tumour size and more so when combined with ZOL.

Keywords: Acridine orange; breast cancer; metastasis; zoledronate.

MeSH terms

  • Acridine Orange / therapeutic use
  • Animals
  • Bone Density Conservation Agents* / therapeutic use
  • Bone Neoplasms* / drug therapy
  • Bone Neoplasms* / secondary
  • Breast Neoplasms* / drug therapy
  • DNA Nucleotidylexotransferase
  • Diphosphonates
  • Female
  • Imidazoles / therapeutic use
  • Mice
  • Osteolysis* / drug therapy
  • X-Ray Microtomography
  • Zoledronic Acid / therapeutic use

Substances

  • Acridine Orange
  • Bone Density Conservation Agents
  • Diphosphonates
  • DNA Nucleotidylexotransferase
  • Imidazoles
  • Zoledronic Acid