Ponatinib reduces viability, migration, and functionality of human endothelial cells

Area of Science:

• Biomedical research
• Molecular biology
• Oncology

Background:

• Tyrosine kinase inhibitors (TKIs) have transformed chronic myeloid leukemia treatment.
• Managing TKI-associated vascular adverse events (VAEs) is now a clinical focus.
• Understanding the mechanisms behind TKI-induced VAEs is crucial for patient safety.

Purpose of the Study:

• To investigate the in vitro effects of TKIs on endothelial cells.
• To elucidate the specific mechanisms of ponatinib-associated vascular adverse events.
• To explore the role of VEGFR2 in ponatinib's effects on angiogenesis.

Main Methods:

• Utilized an in vitro angiogenesis model with human umbilical vein endothelial cells (HUVECs).
• Assessed HUVEC viability, apoptosis, migration, and tube formation.
• Evaluated the impact of ponatinib on endothelial progenitor cell (EPC) function.
• Investigated ponatinib's effects in HUVECs with modified VEGF receptor 2 (VEGFR2) expression.

Main Results:

• Imatinib, nilotinib, and ponatinib reduced HUVEC viability.
• Ponatinib induced apoptosis, inhibited migration, and impaired tube formation in HUVECs at pharmacological concentrations.
• Ponatinib negatively affected endothelial progenitor cell function.
• Ponatinib's detrimental effects on endothelial cell function were less pronounced in VEGFR2-transfected cells.

Conclusions:

• Ponatinib exhibits antiangiogenic properties, potentially through VEGFR2 inhibition.
• This study provides novel insights into the pathogenesis of ponatinib-associated vascular adverse events.
• The findings contribute to understanding the complex mechanisms of TKI-induced VAEs.