ABSTRACT
The mechanisms of VEGF-mediated effects on endothelial cells during cancer development and progression is not clear. In present study the biological effects of VEGF, VEGF-rich culture medium of peritoneal macrophages from mice with Lewis lung carcinoma were studied on MAEC cell line under conditions of unfed culture. We have shown that VEGF increased cell proliferation by the 5th day of culturing vs control and anti-VEGF-treated cells. This effect was associated with increased consumption of glucose and NO production by the 2nd day while decreased on the 5th day of cell culturing. VEGF-mediated NO production was dependent on Ca2+ ions. Block of Ca2+-channels (LaCl3) had more pronounced inhibitory effect vs chelator of Ca2+ ions (EDTA). It was shown that peritoneal macrophages are the main suppliers of VEGF at tumor angiogenesis, as evidenced by the data obtained on model system of endothelial cells synchronized in G0/G1 phase.
Subject(s)
Calcium/metabolism , Carcinoma, Lewis Lung/metabolism , Endothelial Cells/drug effects , Macrophages, Peritoneal/metabolism , Neovascularization, Pathologic/metabolism , Vascular Endothelial Growth Factor A/pharmacology , Animals , Antibodies, Monoclonal/pharmacology , Calcium Channel Blockers/pharmacology , Calcium Channels/metabolism , Carcinoma, Lewis Lung/pathology , Cell Cycle/drug effects , Cell Line, Transformed , Cell Proliferation/drug effects , Cell Survival/drug effects , Coculture Techniques , Culture Media, Conditioned/chemistry , Culture Media, Conditioned/pharmacology , Edetic Acid/pharmacology , Endothelial Cells/cytology , Endothelial Cells/metabolism , Female , Glucose/metabolism , Lanthanum/pharmacology , Macrophages, Peritoneal/drug effects , Macrophages, Peritoneal/pathology , Mice , Neovascularization, Pathologic/pathology , Nitric Oxide/biosynthesis , Primary Cell Culture , Vascular Endothelial Growth Factor A/biosynthesisABSTRACT
The effect of mitokorrectine (complex native oligopeptides isolated from neonatal pig brain) on endothelial cells in culture was investigated. It was revealed that the drug concentration-dependently induces angiogenesis in vitro. Mitogen effect of Mitokorrectine was shown by MTT-test and routine cell count in concentration diapason (0.1-1 mg/ml) which means an increased number of cells by 25 +/- 5% and cell subpopulation of proliferative pool (G2/M+S) 1,8 times in concentration diapason mitokorrectine (0.01-0.05 mg/ml) in comparison with control. In 3-D culture and in stationary phase we detected induction of differentiation of endothelial cells, a decrease the level of NO production and enhancement of glucose metabolism and stimulation of formation of capillary-like tubes.
