Inhibition of phosphoinositide 3-kinase is associated with reduced angiogenesis and an altered expression of angiogenic markers in endothelioma cells.
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) 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.
Angiogenesis Laboratory, Department of Anatomy and Physiology, University of Pretoria, Private Bag X04, Onderstepoort, Tshwane, 0110, South Africa. Electronic address: peace.mabeta@up.ac.za.
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D043925:Angiogenesis Inducing Agents / Q000378:metabolism; D000818:Animals; D001011:Aorta / Q000187:drug effects; D014408:Biomarkers, Tumor / Q000378:metabolism*; D020169:Caspases / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002867:Chromones / Q000494:pharmacology; D006390:Hemangioendothelioma / Q000098:blood supply / Q000188:drug therapy* / Q000201:enzymology* / Q000473:pathology; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D009025:Morpholines / Q000494:pharmacology; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000201:enzymology* / Q000473:pathology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D017207:Rats, Sprague-Dawley
D043925:Angiogenesis Inducing Agents; D014408:Biomarkers, Tumor; D020169:Caspases; D002867:Chromones; D009025:Morpholines; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
Akt; Angiogenesis; Endothelioma; LY294,002; PI3k