Sinensetin suppresses angiogenesis in liver cancer by targeting the VEGF/VEGFR2/AKT signaling pathway.

ABSTRACT: Sinensetin (SIN) is a polymethoxy flavone primarily present in citrus fruits. This compound has demonstrated anticancer activity. However, the underlying mechanism of its action has not been fully understood. The present study investigated the impact of SIN on angiogenesis in a liver cancer model. In a murine xenograft tumor model, SIN inhibited the growth of HepG2/C3A human liver hepatoma cell-derived tumors and reduced the expression levels of platelet/endothelial cell adhesion molecule-1 and VEGF. In HepG2/C3A cells, SIN repressed VEGF expression by downregulating hypoxia-inducible factor expression. In cultured human umbilical vein endothelial cells, SIN increased apoptosis and repressed migration and tube formation. In addition, SIN decreased the phosphorylation of VEGFR2 and inhibited the AKT signaling pathway. Molecular docking demonstrated that the VEGFR2 core domain effectively combined with SIN at various important residues. Collectively, these data suggested that SIN inhibited liver cancer angiogenesis by regulating VEGF/VEGFR2/AKT signaling.

SUBMITTER: Li X 

PROVIDER: S-EPMC9019764 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature