Angiogenesis, the process of new blood vessel formation, is a central mechanism underlying the development of hemangiomas.1,2 Hemangiomas are benign neoplasms of the vasculature frequently encountered in children. 1,2 Growth factors which mediate angiogenesis such as vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) have been implicated in the pathogenesis of hemangiomas.3 Recently we reported on the antiangiogenic effects of bleomycin in vitro in cultured human hemangioma biopsies.4 In the present study we investigated the antiangiogenic effects of bleomycin (0.6-1.2 mg/kg) in vivo in a hemangioma mouse model using C57BL6 female mice. Tumors were induced by injecting mice on the flanks with endothelioma cells. Tumor growth was monitored every second day up to 15 days post treatment. Mice were anaesthetised using 3% Isoflurane. Tissue samples were stained with hematoxylin and eosin for light microscopy, and processed for immunohistochemistry and immunofluorescent microscopy evaluation. Blood samples were collected by cardiac puncture for the measurement of VEGF using ELISA. Analysis of tumor volumes revealed a significant reduction in tumor growth in mice treated with Bleomycin when compared with those treated with buffered saline (n = 5 per group; p<0.05). Low levels of the angiogenic factor VEGF were measured in samples of mice treated with bleomycin. Histological evaluation revealed a reduced microvessel density (MVD) in tumors from bleomycin-treated mice compared to those treated with saline. No tumor growth was observed in baseline mice (the group that was not injected with endothelioma cells). Tumor growth inhibition was associated with the suppression of Flk-1, bcl-2 and Akt activity. Our observations reveal a possible mechanism for the inhibitory effects of bleomycin on hemangiomagenesis, and raise the possibility that the suppression of bcl-2 in particular may provide a therapeutic target for the treatment of vascular tumors of infancy.
37th Congress of IUPS (Birmingham, UK) (2013) Proc 37th IUPS, PCD329
Poster Communications: Low Akt activity, decreased VEGFR-2 expression and bcl-2 suppression are associated with regressing vascular tumors in mice
P. Mabeta1, M. S. Pepper2
1. Anatomy and Physiology, University of Pretoria, Pretoria, South Africa. 2. Immunology, University of Pretoria, Pretoria, South Africa.
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Where applicable, experiments conform with Society ethical requirements.