Inhibition of epidermoid carcinoma A431 cell growth and angiogenesis in nude mice by early and late treatment with a novel dextran derivative.

Abstract

We investigated the effect of a new dextran derivative, phenylacetate carboxymethyl benzylamide dextran (NaPaC), on epidermoid carcinoma A431 cells secreting a large quantity of angiogenic factor, vascular endothelial growth factor (VEGF). In vitro, NaPaC inhibited the proliferation of A431 cells (IC(50)=5 micro M). Also, NaPaC decreased the binding of radiolabelled VEGF(165) to endothelial cells (IC(50)=0.2 micro M). In vivo, we explored the effects of NaPaC (15 mg kg(-1)) on A431 xenograft growth starting the drug administration at the time of tumour cell inoculation (early treatment) and 1 week later, when tumours were well established (late treatment). Early treatment was more efficient on tumour inhibition (70% vs control) than late treatment (50% vs control). Early and late NaPaC-treatment increased the aponecrosis in tumour by 70 and 30%, respectively. Whatever treatment, NaPaC inhibited the intratumour endothelial cell density in the same manner. In contrast, vessel area was decreased only when NaPaC was injected early (35%). These results show that NaPaC has a potent inhibitory effect, dependent on treatment outset, on epidermoid carcinoma growth associated with an intratumour microvascular network diminution and an aponecrosis increase. As this drug is nontoxic at efficient dose, it offers interesting perspectives for the therapy of malignant lesions.

• Authors: M Di Benedetto, A Starzec, R Vassy, G Y Perret, M Crépin, M Kraemer
• Journal: British journal of cancer (Br J Cancer) Vol. 88 Issue 12 Pg. 1987-94 (Jun 16 2003) ISSN: 0007-0920 [Print] England
• PMID: 12799647 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Dextrans
• Endothelial Growth Factors
• Intercellular Signaling Peptides and Proteins
• Lymphokines
• VEGFA protein, human
• Vascular Endothelial Growth Factor A
• Vascular Endothelial Growth Factors
• phenylacetate carboxymethyl benzylamide dextran

Topics

• Animals
• Carcinoma, Squamous Cell (blood supply)
• Cell Division (drug effects)
• Dextrans (pharmacology)
• Endothelial Growth Factors
• Endothelium, Vascular (metabolism)
• Humans
• Intercellular Signaling Peptides and Proteins
• Lymphokines
• Mice
• Mice, Nude
• Neoplasm Transplantation
• Neovascularization, Pathologic
• Time Factors
• Transplantation, Heterologous
• Tumor Cells, Cultured
• Vascular Endothelial Growth Factor A
• Vascular Endothelial Growth Factors