Yang Min, Li Wen-Yun, Xie Jing, Wang Zi-Lin, Wen Yan-Long, Zhao Cun-Chao, Tao Liang, Li Ling-Fei, Tian Yang, Sheng Jun
College of Food Science and Technology, Yunnan Agricultural University, Kunming, China.
National Research and Development Professional Center for Moringa Processing Technology, Yunnan Agricultural University, Kunming, China.
Front Pharmacol. 2021 Apr 19;12:639256. doi: 10.3389/fphar.2021.639256. eCollection 2021.
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 and . 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 . Our further investigations unveiled astragalin gavage significantly reduced the proliferation of colon cancer xenograft in nude mice, 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 and via the NF-κB pathway. Therefore, astragalin maybe become a potential plant-derived antitumor drug for colon cancer.
黄芪苷是一种存在于多种天然植物中的黄酮类化合物。它具有抗炎、抗氧化作用,并且对多种恶性肿瘤细胞类型有抑制作用。然而,其对结肠癌的作用及分子机制仍有待阐明。在本研究中,我们评估了黄芪苷对人结肠癌HCT116细胞增殖和迁移的抑制作用。此外,我们阐明了这些作用的机制。结果表明,黄芪苷通过诱导凋亡(通过调节Bax、Bcl-2、P53、caspase-3、caspase 6、caspase 7、caspase 8、caspase 9蛋白表达)和细胞周期阻滞(通过调节细胞周期蛋白D1、细胞周期蛋白E、P21、P27、细胞周期蛋白依赖性激酶2、细胞周期蛋白依赖性激酶4蛋白表达)显著抑制HCT116细胞的增殖和扩散。此外,黄芪苷通过抑制基质金属蛋白酶(MMP-2、MMP-9)的表达来抑制HCT116细胞迁移。此外,黄芪苷显著下调NF-κB信号通路关键蛋白的表达,并抑制炎性细胞因子TNF-α刺激的NF-κB P65的转录活性,从而抑制结肠癌细胞的生长。我们的进一步研究发现,黄芪苷灌胃显著降低了裸鼠结肠癌异种移植瘤的增殖,实验表明肿瘤生长与肿瘤组织中凋亡蛋白表达降低及NF-κB信号通路活性降低有关。综上所述,我们的结果表明黄芪苷通过NF-κB途径抑制结肠癌细胞的增殖和生长。因此,黄芪苷可能成为一种潜在的植物源结肠癌抗肿瘤药物。