Abstract
Angiogenesis is critical for the growth and metastasis of triple-negative breast cancer (TNBC) and its inhibition reduces the risk of progression of metastatic TNBC. In this study, we investigated that LYG-202, a flavonoid with a piperazine substitution, inhibited angiogenesis induced by conditioned media (CM) from MDA-MB-231 cells under hypoxia and revealed its underlying mechanism. The results showed that LYG-202 decreased CXCL12 secretion and CXCR7 expression, leading to suppression of its downstream ERK/AKT/nuclear factor kappa B (NF-κB) signaling, which eventually decreased the expression of MMP-2, MMP-9, RhoA and increased VE-cadherin expression in EA.hy 926 cells treated with CM from MDA-MB-231 cells under hypoxia. The decreased migration ability, increased cell adhesion and inhibited CXCR7 pathway by LYG-202 could also be reproduced in human umbilical vein endothelial cells. More importantly, LYG-202 also inhibited tumor angiogenesis and tumor growth of human breast cancer MDA-MB-231 cells in nude mice through CXCL12/CXCR7 pathway. In summary, LYG-202 is a potential agent to prohibit tumor angiogenesis through inhibiting the activation of endothelial cells.
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