VDX-111 targets proliferative pathways in canine cancer cell lines

PLoS One. 2024 May 21;19(5):e0303470. doi: 10.1371/journal.pone.0303470. eCollection 2024.

Abstract

VDX-111 (also identified as AMPI-109) is a vitamin D derivative which has shown anticancer activity. To further assess the function of this compound against multiple cancer types, we examined the efficacy of VDX-111 against a panel of 30 well characterized canine cancer cell lines. Across a variety of cancer types, VDX-111 induced widely variable growth inhibition, cell death, and migration inhibition, at concentrations ranging from 10 nM to 1 μM. Growth inhibition sensitivity did not correlate strongly with tumor cell histotype; however, it was significantly correlated with the expression of genes in multiple cell signaling pathways, including the MAPK and PI3K-AKT pathways. We confirmed inhibition of these signaling pathways as likely participants in the effects of VDX-111. These results suggest that a subset of canine tumors may be sensitive to treatment with VDX-111, and suggests possible predictive markers of drug sensitivity and pharmacodynamic biomarkers of drug exposure that could be employed in future clinical trials.

MeSH terms

  • Animals
  • Antineoplastic Agents* / pharmacology
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation* / drug effects
  • Dog Diseases / drug therapy
  • Dog Diseases / metabolism
  • Dogs
  • Gene Expression Regulation, Neoplastic / drug effects
  • Neoplasms / drug therapy
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Signal Transduction* / drug effects
  • Vitamin D / pharmacology

Substances

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