Vasostatin inhibits VEGF-induced endothelial cell proliferation, tube formation and induces cell apoptosis under oxygen deprivation.
Anti-angiogenesis treatment has been a promising new form of cancer therapy. Endothelial cells are critical for vascular homeostasis and play important roles in angiogenesis, vascular and tissue remodeling. Vasostatin, the 180 amino acid N-terminal fragment of the calreticulin protein, is reported to be a potent endogenous inhibitor of angiogenesis, suppressing tumor growth. However, the mechanism of these effects has not been sufficiently investigated. This study was performed to investigate the possible mechanism of vasostatin effects on primary cultured human umbilical vein endothelial cells (HUVEC). We found that vasostatin could inhibit the cell viability of HUVEC and induce cell apoptosis through mitochondrial pathways via activation of caspase-3 under oxygen deprivation conditions. Meanwhile, vasostatin also inhibited vascular endothelial growth factor-induced proliferation and tube formation of HUVEC. The possible mechanism of vasostatin-inhibited proliferation of HUVEC could be through down-regulation of endothelial nitric oxide synthase. These findings suggest that vasostatin could regulate endothelial cell function and might be used in anti-angiogenesis treatment.
Shanghai Changning Maternity and Infant Health Hospital, 773 Wuyi Road, Shanghai 200051, China. cmihh2012@163.com.
Qun
Q
Shu
Shanghai Changning Maternity and Infant Health Hospital, 773 Wuyi Road, Shanghai 200051, China. liwenjiao2008@163.com.
Wenjiao
W
Li
Shanghai Changning Maternity and Infant Health Hospital, 773 Wuyi Road, Shanghai 200051, China. lihaichuan_happy@163.com.
Haichuan
H
Li
School of Life Sciences, Fudan University, 220 Handan Road, Shanghai 200433, China. sungang122012@163.com.
Gang
G
Sun
D017209:Apoptosis / Q000187:drug effects*; D037282:Calreticulin / Q000494:pharmacology*; D053148:Caspase 3 / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D018919:Neovascularization, Physiologic / Q000187:drug effects; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism; D010100:Oxygen / Q000737:chemistry / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D037282:Calreticulin; D010446:Peptide Fragments; D019253:Proto-Oncogene Proteins c-bcl-2; D042461:Vascular Endothelial Growth Factor A; D051028:bcl-2-Associated X Protein; C121986:vasostatin; D052250:Nitric Oxide Synthase Type III; D053148:Caspase 3; D010100:Oxygen