Study on the Mechanism of Diosgenin Targeting STAT3 to Inhibit Colon Cancer Proliferation and Migration.

To elucidate regulatory effects and molecular mechanisms of diosgenin on colon cancer, this study administered diosgenin at concentrations of 10 (low), 50 (medium), and 100 µmol/L (high concentration group) at the cell level, respectively. EdU, colony formation, and Transwell assays were implemented to determine SW480 cellular proliferation and migration. Assays of flow cytometry and TUNEL were employed to estimate cell apoptosis. Additionally, nude mouse tumorigenesis assay was used to further verify the regulatory function of diosgenin on colon cancer. The target protein of diosgenin was predicted via molecular docking. The results showed that all three concentrations of diosgenin could reduce colon cancer cellular proliferation and migration, and after diosgenin treatment, colon cancer cellular apoptosis was markedly increased, and the 100 µmol/L diosgenin group produced the most satisfactory inhibition on colon cancer cell proliferation. Ki67 expression was markedly reduced whereas those of Bax and caspase3 were greatly increased after diosgenin treatment. The nude mouse tumorigenesis assay indicated that the parameters of tumorous volume and mass of diosgenin treatment group were greatly decreased as compared to control, and as the concentration of diosgenin increased, the inhibitory effect was more significant. Molecular docking indicated that STAT3 served as a target protein of diosgenin. Moreover, after diosgenin treatment on colon cancer cells, the STAT3 expression was markedly reduced. The STAT3 overexpression would counteract the inhibitory effect of 50 µmol/L diosgenin in both suppressing colon cancer cellular proliferation and migration and promoting apoptosis. Taken together, all our outcomes demonstrated the diosgenin effects in not only inhibiting colon cancer cellular proliferation and migration but also promoting cancerous cellular apoptosis. Diosgenin is a regulatory player in targeting and regulating STAT3.

Ai-Tong-An-Gao-Ji and Fisetin Inhibit Tumor Cell Growth in Rat CIBP Models by Inhibiting the AKT/HIF-1α Signaling Pathway.

BACKGROUND: Ai-Tong-An-Gao-Ji (ATAGJ) has been extensively applied for acute bone cancer pain treatment with a satisfactory efficacy, while the specific mechanisms remain unclear and require further investigation. METHODS: Overlapped genes of ATAGJ and CIBP obtained from SwissTargetPrediction website and GeneCards database were presented as a Venn diagram. A network diagram of drug-component-target was further established using the Cytoscape 3.6.0 software. The effect of fisetin on Walker 256 cell proliferation was observed by clone formation assay and EDU assay, and the interaction between fisetin and AKT was revealed using the immunoprecipitation assay. Effects of fisetin on AKT/HIF-1α signaling pathway in Walker 256 cells were ultimately detected using Western blot and qPCR assays. RESULTS: The key component fisetin and core target gene AKT were sorted out using the drug-component-target network with a binding energy between fisetin and AKT less than -5 kcal/mol. Clone formation assay and EDU assay showed that fisetin substantially suppressed the proliferation of Walker 256 cells. Immunoprecipitation assay results revealed that the combination of fisetin and AKT decreased the level of AKT/HIF-1α signaling pathway of Walker 256 cells. CONCLUSIONS: The fisetin of ATAGJ can markedly suppress Walker 256 cells, and the mechanisms may be intimately associated with the combination of fisetin and AKT. Furthermore, fisetin decreased the level of p-AKT and inhibited the expression of the AKT/HIF-1α signaling pathway.