Abstract
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.
Highlights
Angiogenesis plays a critical role in the growth and spread of cancer as an adequate blood supply is necessary for tumor growth and invasion in normal tissues [1,2]
The purity of primary cultured human umbilical vein endothelial cells (HUVEC) was identified by flow cytometry (CD31+, CD34+, CD45−, CD56−, data was not shown)
Vasostatin-induced inhibition of tube formation was reversed by eNOS overexpression. Together these results indicate that the vasostatin-induced inhibitory effect on vascular endothelial growth factor (VEGF)-induced cell proliferation and tube formation in HUVEC could be via down-regulation of eNOS expression
Summary
Angiogenesis plays a critical role in the growth and spread of cancer as an adequate blood supply is necessary for tumor growth and invasion in normal tissues [1,2]. Agents that block the growth of a tumor’s blood vessels promote the regression or dormancy of established tumors and anti-angiogenesis treatment has been a promising new form of cancer therapy [3]. It is known that endothelial cells are critical for vascular homeostasis and play important roles in angiogenesis, vascular and tissue remodeling. Since Pike et al first reported in 1998 [4], vasostatin, the 180 amino acid N-terminal fragment of the calreticulin protein, has been recognized as a potent endogenous inhibitor of angiogenesis to suppress tumor growth. A growing body of evidence supports the beneficial effect of anti-angiogenesis of vasostatin. Cancer gene therapy based on the intramuscular delivery of plasmid
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