Abstract:
The phosphoinositide 3-kinase (PI3k) signaling pathway is involved in the regulation of
numerous cellular activities. The pathway has also been implicated in the development of
various tumors. In the context of vascular tumors, the role of the PI3k signaling still needs to
be established. In the present study the effects of blocking PI3k activation on endothelioma
cells derived from mice with vascular tumors were investigated using the crystal violet assay,
real time cell analysis, light microscopy, the aorta ring assay and antibody arrays. The
suppression of PI3k led to the inhibition of cell growth, cell migration, as well as
angiogenesis. The inhibition of these processes correlated with low Akt activity. Antibody
array analysis revealed that there was a suppression of several proangiogenic molecules,
including Eotaxin-1 and basic fibroblast growth factor (bFGF) in cultures treated with
LY294,002, an inhibitor of PI3k. At the same time, LY294,002 increased the expression of
platelet factor 4 (PF4), interleukin (IL)-12 p40/70 and the Fas ligand (FasL), molecules which
have antiangiogenic properties. The results suggest that PI3k may play a role in the
expression of some of the key regulatory molecules involved in angiogenesis, and perhaps in
the growth of endotheliomas. As such, it is plausible that the PI3k/Akt pathway may be a
target for therapeutic molecules designed for the treatment of endothelial tumors.
