Amniotic membrane promotes doxorubicin potency by suppressing SH-SY5Y neuroblastoma cell angiogenesis

Area of Science:

• Oncology
• Cell Biology
• Biochemistry

Background:

• Doxorubicin (DOX) is a key neuroblastoma (NB) treatment, but its efficacy is limited by side effects.
• Previous research indicated DOX promotes NB cell angiogenesis via the PHD-2/HIF-1α pathway.
• Human amniotic membrane extract (hAM) contains anti-cancer and anti-angiogenic proteins, suggesting its potential as an adjuvant therapy.

Purpose of the Study:

• To investigate human amniotic membrane extract (hAME) as an adjuvant therapy for neuroblastoma (NB).
• To evaluate the combined effects of hAME and doxorubicin (DOX) on NB cell progression and angiogenesis.
• To assess the safety and efficacy of hAME + DOX (D+E) treatment on NB hallmarks and normal cells.

Main Methods:

• Utilized cellular, molecular, and biochemical assays to assess D+E treatment effects on SH-SY5Y NB cells.
• Evaluated proliferation, cell cycle, angiogenesis, invasiveness, differentiation, and bioenergetics.
• Assessed neo-vascularization in a chick embryo model.

Main Results:

• D+E treatment significantly suppressed SH-SY5Y NB cell proliferation, induced cell cycle arrest, and reduced viability.
• The combination therapy protected normal bone marrow stem cells and human skin fibroblasts.
• D+E treatment inhibited NB cell invasiveness, promoted mesenchymal-to-epithelial transition (MET), modulated cellular respiration, and abrogated DOX-induced pro-angiogenic effects.

Conclusions:

• hAME demonstrates potential as a safe and effective adjuvant therapy for neuroblastoma (NB).
• The combination of hAME and DOX targets multiple hallmarks of NB, including proliferation and angiogenesis.
• This approach may offer an improved treatment strategy for NB patients.