Department of Genetic Engineering, Kyung Hee University, Yongin, Korea.
Graduate School of Biotechnology, Kyung Hee University, Yongin, Korea.
Phytother Res. 2020 Feb;34(2):359-367. doi: 10.1002/ptr.6526. Epub 2019 Nov 3.
Tumor angiogenesis and lymphangiogenesis are important processes in tumor progression and metastasis. The inhibitory effects of 3-O-acetyloleanolic acid (3AOA), a pentacyclic triterpenoid compound isolated from Vigna sinensis K., on tumor-induced angiogenesis and lymphangiogenesis in vitro and in vivo were studied. Angiopoietin-1 is an important angiogenic and lymphangiogenic factor secreted from colon carcinoma CT-26 cells under hypoxia conditions. 3AOA inhibited proliferation, migration, and tube formation of angiopoietin-1-treated human umbilical vein endothelial cells (HUVEC) and human lymphatic microvascular endothelial cells (HLMEC). 3AOA reduced angiogenesis and lymphangiogenesis in angiopoietin-1-stimulated Matrigel plugs. Also, 3AOA inhibited tumor growth and tumor-induced angiogenesis and lymphangiogenesis in an angiopoietin-1-induced CT-26 allograft colon carcinoma animal model. 3AOA inhibited activation of the angiopoietin-1 receptor Tie-2 and activation of the downstream signaling factors FAK, AKT, and ERK1/2 that are involved in the angiopoietin-1/Tie-2-signaling pathway. Thus, 3AOA has an inhibitory effect on angiogenesis and lymphangiogenesis induced by angiopoietin-1 both in vitro and in vivo, and the inhibitory effect of 3AOA is probably due to suppression of angiopoietin-1/Tie-2 signaling in HUVEC and HLMEC.
肿瘤血管生成和淋巴管生成是肿瘤进展和转移的重要过程。从豇豆中分离得到的五环三萜化合物 3-O-乙酰齐墩果酸（3AOA）对肿瘤诱导的血管生成和淋巴管生成的体外和体内抑制作用进行了研究。血管生成素-1 是缺氧条件下结肠癌细胞 CT-26 分泌的重要血管生成和淋巴管生成因子。3AOA 抑制了血管生成素-1 处理的人脐静脉内皮细胞（HUVEC）和人淋巴管微血管内皮细胞（HLMEC）的增殖、迁移和管形成。3AOA 减少了血管生成素-1 刺激的 Matrigel 塞中的血管生成和淋巴管生成。此外，3AOA 抑制了血管生成素-1 诱导的 CT-26 同种异体结肠癌动物模型中的肿瘤生长和肿瘤诱导的血管生成和淋巴管生成。3AOA 抑制了血管生成素-1 受体 Tie-2 的激活以及参与血管生成素-1/Tie-2 信号通路的下游信号因子 FAK、AKT 和 ERK1/2 的激活。因此，3AOA 对血管生成素-1 诱导的血管生成和淋巴管生成具有体外和体内的抑制作用，3AOA 的抑制作用可能是由于抑制了 HUVEC 和 HLMEC 中的血管生成素-1/Tie-2 信号。
