20(S)-Ginsenoside Rg3 regulates the Hedgehog signaling pathway to inhibit proliferation and epithelial-mesenchymal transition of lung cancer cells

20(S)-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 pi-pi 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.