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酸枣仁皂苷B通过阻断VEGFR2信号通路抑制血管生成和肿瘤生长。

Jujuboside B suppresses angiogenesis and tumor growth via blocking VEGFR2 signaling pathway.

作者信息

Zhang Pan, Lai Xing, Zhu Mao-Hua, Shi Jiangpei, Pan Hong, Huang Yanhu, Guo Run-Jie, Lu Qin, Fang Chao, Zhao Mei

机构信息

Department of Pharmacy, Shanghai University of Medicine & Health Sciences, Shanghai, 201318, China.

Hongqiao International Institute of Medicine, Tongren Hospital and State Key Laboratory of Systems Medicine for Cancer, Department of Pharmacology and Chemical Biology, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai, 200025, China.

出版信息

Heliyon. 2023 Jun 7;9(6):e17072. doi: 10.1016/j.heliyon.2023.e17072. eCollection 2023 Jun.

Abstract

Jujuboside B (JuB), one of the main active triterpenoid saponins from the traditional Chinese medicine possesses a wide range of pharmacological activities. However, it is unknown whether JuB can inhibit tumor angiogenesis, a crucial step in solid tumor growth. In this study, we found that JuB significantly inhibited the proliferation, migration, and tube formation of human umbilical vein endothelial cells in a dose-dependent manner. JuB also suppressed angiogenesis in chick embryo chorioallantoic membranes and Matrigel plugs. Moreover, through angiogenesis inhibition, JuB delayed the growth of human HCT-15 colorectal cancer xenograft in mice. Western blot assay demonstrated that JuB inhibited the phosphorylation of VEGFR2 and its key downstream protein kinases, such as Akt, FAK, Src, and PLCγ1. In conclusion, the antiangiogenic potency and molecular mechanism of JuB are revealed for the first time, indicating that this triterpene saponin may be further explored as a potential drug candidate or lead compound for antiangiogenic cancer therapy.

摘要

酸枣仁皂苷B(JuB)是一种源自传统中药的主要活性三萜皂苷,具有广泛的药理活性。然而,JuB是否能抑制肿瘤血管生成(实体瘤生长中的关键步骤)尚不清楚。在本研究中,我们发现JuB以剂量依赖性方式显著抑制人脐静脉内皮细胞的增殖、迁移和管腔形成。JuB还抑制鸡胚绒毛尿囊膜和基质胶塞中的血管生成。此外,通过抑制血管生成,JuB延缓了人HCT - 15结直肠癌异种移植瘤在小鼠体内的生长。蛋白质免疫印迹分析表明,JuB抑制VEGFR2及其关键下游蛋白激酶(如Akt、FAK、Src和PLCγ1)的磷酸化。总之,首次揭示了JuB的抗血管生成潜力及其分子机制,表明这种三萜皂苷可作为抗血管生成癌症治疗的潜在候选药物或先导化合物进行进一步研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/392d/10361242/db44987703a3/gr1.jpg

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