Astragalin Inhibits the Proliferation and Migration of Human Colon Cancer HCT116 Cells by Regulating the NF-κB Signaling Pathway

黄芪甲素 细胞周期蛋白D1 细胞生长 细胞凋亡 癌症研究 NF-κB 化学 半胱氨酸蛋白酶8 体内 癌细胞 信号转导 细胞生物学 细胞周期 半胱氨酸蛋白酶3 生物 癌症 生物化学 程序性细胞死亡 抗氧化剂 类黄酮 生物技术 遗传学 山奈酚
作者
Min Yang,Wen-Yun Li,Jing Xie,Zilin Wang,Yanlong Wen,Zhao Chun-hua,Liang Tao,Lingfei Li,Tian Yang,Jun Sheng
出处
期刊:Frontiers in Pharmacology [Frontiers Media SA]
卷期号:12 被引量:22
标识
DOI:10.3389/fphar.2021.639256
摘要

Astragalin is a flavonoid found in a variety of natural plants. It has anti-inflammatory, anti-oxidant effects and has inhibited effects against several malignant tumor cell types. However, its effects on colon cancer and the molecular mechanisms have remained to be elucidated. In this study, we evaluated the inhibitory effect of astragalin on proliferation and migration of human colon cancer HCT116 cells in vitro and in vivo . Furthermore, we elucidated the mechanism of these effects. The results showed that astragalin significantly inhibited the proliferation and diffusion of HCT116 cells by induced apoptosis (by modulation of Bax, Bcl-2, P53, caspase-3, caspase 6, caspase 7, caspase 8, caspase 9 protein express) and cell cycle arrest (by modulation of Cyclin D1, Cyclin E, P21, P27, CDK2, CDK4 protein express). Moreover, astragalin suppressed HCT116 cell migration by inhibiting the expression of matrix metalloproteinases (MMP-2, MMP-9). In addition, astragalin significantly downregulated the expression of key proteins in the NF-κB signaling pathway and inhibited the transcriptional activity of NF-κB P65 stimulated with inflammatory cytokines TNF-α, thereby inhibiting the growth of colon cancer cells in vitro . Our further investigations unveiled astragalin gavage significantly reduced the proliferation of colon cancer xenograft in nude mice, in vivo experiments showed that tumor growth was related to decreased expression of apoptotic proteins in tumor tissues and decreased activity of the NF-κB signaling pathway. In summary, our results indicated that astragalin inhibits the proliferation and growth of colon cancer cells in vivo and in vitro via the NF-κB pathway. Therefore, astragalin maybe become a potential plant-derived antitumor drug for colon cancer.
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