Department of Hospital Pharmacy, Suqian First Hospital,120 Suzhi road, Suqian 223800, People's Republic of China.
Department of Hospital Pharmacy, Suqian First Hospital,120 Suzhi road, Suqian 223800, People's Republic of China;, Email:
Pharmazie. 2021 Sep 1;76(9):431-436. doi: 10.1691/ph.2021.1573.
20()-Ginsenoside Rg3 (S-Rg3) has good antitumor activity and has been used in clinical oral antitumor therapy. However, the effect of S-Rg3 on the Hedgehog (Hh) signaling pathway has not been reported. In this study, we used CCK8, cell wound healing, Transwell, and western blotting assays as well as small interfering RNA to decrease GLI1 protein expression to investigate the effect of S-Rg3 on the Hh pathway in A549 cells. The results showed that S-Rg3 substantially inhibited the proliferation, migration, and invasion of A549 cells in a concentration-dependent manner. Furthermore, S-Rg3 had significant regulatory effects on PTCH1 and GLI1, key proteins in the Hh pathway, causing significant upregulation of PTCH1 levels and downregulation of GLI1 expression. After silencing the Hh signaling pathway, the inhibitory effect of S-Rg3 administration on the expression of epithelial mesenchymal transition-related proteins was further enhanced. Molecular dynamics simulations showed that Rg3 molecules could bind stably to PTCH1 protein through hydrophobic interactions, hydrogen bonds, and π-π stacking forces. Thus, S-Rg3 can regulate Hh signaling pathway transduction in A549 cells to inhibit lung cancer cell proliferation, migration, invasion, and epithelial mesenchymal transition.
20()-人参皂苷 Rg3（S-Rg3）具有良好的抗肿瘤活性，已用于临床口服抗肿瘤治疗。然而，S-Rg3 对 Hedgehog（Hh）信号通路的影响尚未报道。在本研究中，我们使用 CCK8、细胞划痕愈合、Transwell 和 Western blot 检测以及小干扰 RNA 降低 GLI1 蛋白表达来研究 S-Rg3 对 A549 细胞中 Hh 通路的影响。结果表明，S-Rg3 以浓度依赖的方式显著抑制 A549 细胞的增殖、迁移和侵袭。此外，S-Rg3 对 Hh 通路中的关键蛋白 PTCH1 和 GLI1 具有显著的调节作用，导致 PTCH1 水平显著上调，GLI1 表达下调。沉默 Hh 信号通路后，S-Rg3 给药对上皮间质转化相关蛋白表达的抑制作用进一步增强。分子动力学模拟表明，Rg3 分子可以通过疏水相互作用、氢键和 π-π 堆积力与 PTCH1 蛋白稳定结合。因此，S-Rg3 可以调节 A549 细胞中的 Hh 信号通路转导，抑制肺癌细胞增殖、迁移、侵袭和上皮间质转化。
