Auranofin Suppresses the Growth of Canine Mammary Tumour Cells and Induces Apoptosis via the PI3K/AKT Pathway

Vet Comp Oncol. 2024 Dec;22(4):555-565. doi: 10.1111/vco.13005. Epub 2024 Sep 2.

Abstract

Canine mammary gland tumour (CMT) is the most common spontaneous tumour in intact female dogs and often exhibits metastases. Auranofin (AF) is a gold complex used for treating rheumatism. The excellent anti-tumour ability of AF has been demonstrated in various types of human and canine tumours. In this study, five CMT cell lines (CIPp, CMT-7364, CHMp, CIPm and CTBp) and three CMT primary cells (G7894, L1883 and L6783) were used to explore the anti-tumour effect of AF on CMT. Two CMT cell lines (CIPp and CMT-7364) were used to search the underlying mechanism of the effect of AF on CMT. The results showed that AF inhibited the growth, migration, invasion, and colony formation abilities of CMT cells. Additionally, the growth of CMT in a 3D cell culture model was effectively suppressed by AF. Furthermore, AF induced cell apoptosis of CMT cells via the PI3K/AKT pathway. In conclusion, AF effectively induces CMT apoptosis by regulating the PI3K/AKT pathway, indicating that AF should be explored as a potential CMT treatment in future studies.

Keywords: 3D cell culture; CMT; PI3K/AKT; apoptosis; auranofin.

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Apoptosis* / drug effects
  • Auranofin* / pharmacology
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Dog Diseases* / drug therapy
  • Dogs
  • Female
  • Mammary Neoplasms, Animal* / drug therapy
  • Phosphatidylinositol 3-Kinases* / metabolism
  • Proto-Oncogene Proteins c-akt* / metabolism
  • Signal Transduction / drug effects

Substances

  • Proto-Oncogene Proteins c-akt
  • Phosphatidylinositol 3-Kinases
  • Auranofin
  • Antineoplastic Agents