Li Xiao, Li Yan, Wang Yuan, Liu Fuhong, Liu Yanjun, Liang Jiangjiu, Zhan Rucai, Wu Yue, Ren He, Zhang Xiuyuan, Liu Ju
College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, Shangdong 250355, P.R. China.
Laboratory of Microvascular Medicine, Medical Research Center, The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital, Jinan, Shandong 250014, P.R. China.
Exp Ther Med. 2022 May;23(5):360. doi: 10.3892/etm.2022.11287. Epub 2022 Mar 31.
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.
川陈皮素（SIN）是一种主要存在于柑橘类水果中的多甲氧基黄酮。该化合物已显示出抗癌活性。然而，其作用的潜在机制尚未完全了解。本研究调查了SIN对肝癌模型中血管生成的影响。在小鼠异种移植肿瘤模型中，SIN抑制了HepG2/C3A人肝癌细胞衍生肿瘤的生长，并降低了血小板/内皮细胞黏附分子-1和VEGF的表达水平。在HepG2/C3A细胞中，SIN通过下调缺氧诱导因子表达来抑制VEGF表达。在培养的人脐静脉内皮细胞中，SIN增加细胞凋亡并抑制迁移和管腔形成。此外，SIN降低了VEGFR2的磷酸化并抑制了AKT信号通路。分子对接表明，VEGFR2核心结构域在多个重要残基处与SIN有效结合。总的来说，这些数据表明SIN通过调节VEGF/VEGFR2/AKT信号通路抑制肝癌血管生成。
