PHD-2/HIF-1α axis mediates doxorubicin-induced angiogenesis in SH-SY5Y neuroblastoma microenvironment: a potential

Ahmed M Abou-Shanab1,2, Ola A Gaser1,2, Noha Galal2

  • 1Center of Excellence for Stem Cells and Regenerative Medicine, Zewail City of Science and Technology, Giza, 12578, Egypt.

Scientific Reports
|March 3, 2025
PubMed

Insights

Doxorubicin, a neuroblastoma treatment, unexpectedly promotes blood vessel growth by upregulating pro-angiogenic factors and activating pathways like Pi3K, suggesting new therapeutic strategies.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Neuroblastoma (NB) treatment response and microenvironment influence are not fully understood.
  • Doxorubicin is a common chemotherapeutic agent for NB.

Purpose of the Study:

  • To investigate the molecular mechanisms by which doxorubicin affects the SH-SY5Y NB cell microenvironment.
  • To determine if doxorubicin induces pro-angiogenic responses in NB cells.

Main Methods:

  • SH-SY5Y cells were treated with doxorubicin.
  • Co-culture systems with human umbilical vein endothelial cells (HUVECs) were used.
  • In-ovo studies, molecular docking, simulations, and bioinformatics analyses were performed.

Main Results:

  • Doxorubicin reduced SH-SY5Y cell proliferation but increased pro-angiogenic factors (VEGF, PDGF, MMP-2) and nitric oxide.
  • HUVECs showed enhanced proliferation, migration, tube formation, and nitric oxide production.
  • In-ovo studies confirmed doxorubicin-induced neo-angiogenesis; HIF-1α stabilization and Pi3K pathway activation were observed.

Conclusions:

  • Doxorubicin unexpectedly induces a pro-angiogenic response in the NB microenvironment.
  • Targeting PHD-2 and utilizing multi-modal therapies may offer improved NB treatment outcomes.

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