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Transfer of Manipulated Tumor-associated Neutrophils into Tumor-Bearing Mice to Study their Angiogenic Potential In Vivo
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Synergistic inhibition of human neuroblastoma-related angiogenesis by vinblastine and rapamycin

Danilo Marimpietri1, Beatrice Nico, Angelo Vacca

  • 1Differentiation Therapy Unit Laboratory of Oncology, G Gaslini Childrens' Hospital, Genoa 16148, and Department of Human Anatomy and Histology, University of Bari Medical School, Italy.

Oncogene
|July 12, 2005
PubMed

Insights

Low doses of vinblastine (VBL) and rapamycin (RAP) synergistically inhibit neuroblastoma (NB) angiogenesis. This combination therapy shows promise for novel NB treatment strategies by targeting tumor blood vessel formation.

Area of Science:

  • Oncology
  • Pharmacology
  • Cell Biology

Background:

  • Neuroblastoma (NB) is a pediatric cancer characterized by rapid tumor growth and metastasis.
  • Angiogenesis, the formation of new blood vessels, is crucial for tumor progression in NB.
  • Existing therapies often have significant side effects, necessitating the exploration of novel treatment approaches.

Purpose of the Study:

  • To investigate the synergistic antiangiogenic effects of low-dose vinblastine (VBL) and rapamycin (RAP) in neuroblastoma (NB).
  • To evaluate the impact of VBL and RAP combination on endothelial cell growth, apoptosis, and cell cycle progression.
  • To assess the in vivo efficacy of the drug combination in inhibiting NB-associated angiogenesis.

Main Methods:

  • In vitro studies included endothelial cell proliferation assays, TUNEL assays, and cell cycle analysis.
  • In vivo assessment utilized the chick embryo chorioallantoic membrane (CAM) assay.
  • Human NB cell line (HTLA-230) conditioned medium, NB tumor xenografts, and biopsy specimens were used to model NB angiogenesis.

Main Results:

  • Both VBL and RAP individually inhibited endothelial cell growth in a dose- and time-dependent manner.
  • A significant synergistic antiangiogenic effect was observed when VBL and RAP were combined at very low doses.
  • The combination therapy induced synergistic apoptosis and cell cycle arrest in endothelial cells, with enhanced morphological changes.
  • In vivo CAM assays confirmed that the drug combination significantly inhibited angiogenic responses induced by NB models.

Conclusions:

  • Low-dose VBL and RAP exhibit synergistic antiangiogenic activity against neuroblastoma.
  • The combination therapy effectively inhibits endothelial cell proliferation, induces apoptosis, and disrupts angiogenesis.
  • This finding suggests a potential new therapeutic strategy for neuroblastoma treatment utilizing frequent, low-dose administration of VBL and RAP.

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