title: Inhibition of hemangioma development in a syngeneic mouse model correlates with bcl-2 suppression and the inhibition of Akt kinase activity.
abstract: BACKGROUND
  Hemangiomas are benign vascular tumors that are characterised by excessive angiogenesis. While there is no definitive treatment for these tumors, several angiogenesis inhibitors, including bleomycin, have been employed. To better understand the mechanism of bleomycin in accelerating haemangioma regression, we investigated the effects of the drug on hemangiomagenesis using a previously described mouse hemangioma model.
  
  
  METHODS
  The effects of bleomycin were tested in mice injected with endothelioma cells to induce hemangioma development. At termination, tissue samples from bleomycin-treated and control mice were stained with hematoxylin and eosin for histological examination. Bcl-2, flk-1 and vWF expression were studied by immunofluorescence microscopy. Hematological analysis was undertaken using a hemocounter. Akt activity was analyzed in tissue homogenates and endothelioma cells using ELISA. Also, caspase activity was analysed in endothelioma cells by ELISA.
  
  
  RESULTS
  Bleomycin inhibited tumor growth in vivo in a dose-dependant manner. Our findings also revealed that bleomycin inhibited Akt activation and suppressed bcl-2. In vitro bleomycin increased caspase activation.
  
  
  CONCLUSIONS
  Our observations reveal possible mechanisms for the inhibitory effects of bleomycin on hemangiomagenesis, and raise the possibility that bcl-2 might be an important therapeutic target in the treatment of hemangiomas.
authors.affiliation: Department of Physiology, Faculty of Health Sciences, University of Pretoria, P.O. Box 2034, Pretoria 0001, South Africa. peace.mabeta@up.ac.za
authors.forename: Peace
authors.initials: P
authors.lastname: Mabeta
authors.forename: Michael S
authors.initials: MS
authors.lastname: Pepper
mesh_terms: D000818:Animals; D001761:Bleomycin / Q000494:pharmacology / Q000627:therapeutic use; D020169:Caspases / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000473:pathology*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D057075:Enzyme Assays; D005260:Female; D005455:Fluorescent Antibody Technique; D006391:Hemangioma / Q000097:blood / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D021381:Protein Transport / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors* / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D013194:Staining and Labeling; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism; D014841:von Willebrand Factor / Q000378:metabolism
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2; D014841:von Willebrand Factor; D001761:Bleomycin; D040301:Vascular Endothelial Growth Factor Receptor-2; D051057:Proto-Oncogene Proteins c-akt; D020169:Caspases