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.
MATERIALS AND 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.
CONCLUSION: 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.