Effect Of K562 Cell Conditioned Medium On Redox State In Endothelial Cells And Its Significance On Tumor Angiogenesis

There have been many experimental studies of antiangiogenic therapy of tumor which targeted a simple molecule of tumor vascular endothelial cell. These research results always have various defects on anti-tumor therapy because tumor angiogenesis is regulated by a complicated network.Reduction/oxidation(redox) reactions play a central role in the regulation of various cell functions through the cellular signaling system. When the cellular redox state changes, cell functions will change. Tumor vascular endothelial cell proliferation can be activated by the increased pro-angiogenic molecules secreted by tumor cells.In contrast, normal tissue vascular endothelial cells are always of statical condition. The objective of this paper is to investigate whether there are difference of cellular redox state between tumor vasular endothelial cells and normal tissue vascular endothelial cells, and to explore the signficance of that diference if existed.To simulate the condition in which tumor vascular endothelial cells proliferate, the tumor conditioned media from cultured K562 cells, a chronic myelogenous leukemia cell line, were added to human umbilical vein endothelial cells.Cellular redox state and cell viability of endothelial cells under various condition were analyzed. Oxidized and reduced glutathione, coenzyme II were selected as markers of cellular redox state.Our study showed that not only the proliferation but also the cellular redox state of human umbilical vein endothelial cells could be affected by conditioned medium from K562 cells. Conditioned medium from K562 cells could promote the viability of human umbilical vein endothelial cells and the concentration of intracellular GSI^ GSSG^ NADPEL NADP+. Correlation analysis showed that there was a positive correlation between the viability of human umbilical vein endothelial cells and the concentration of intracellular GSH, GSSG, NADPH, NADP+ when endothelial cells was cultured with conditioned medium from K562 cells.Oxidative stress of endothelial cells could be induced by buthionine sulfoxine, a specific inhibitor of redued glutathione synthetase, and which was related with the decrease of endothelial cell viability. Importantly, the sensitivity of endothelial cells cultured with K562 cell conditioned medium to buthionine sulfoxine was increased.Thus,our results showed that the redox state of endothelial cell could be changed by tumor cells. The antioxidative capability and oxidative stress of endothelial cell could be promoted by tumor cells while the viability of endothelial cells was also promoted at the same time. When the antioxidative capability of endothelial cells was decreased, tumor cells inhibited the proliferation of endothelial cells instead of promoting it. This provided a novel strategy for antiangiogenic therapy of tumor.