Sophoridine exerts tumor-suppressive activities via promoting ESRRG-mediated β-catenin degradation in gastric cancer

Abstract Background: This study ought to further explore the anti-tumor effects of Sophoridine on gastric cancer cells. Methods: Cell viability assay (CCK-8 assay) was used to measure the IC50 values of Sophoridine on gastirc cancer AGS and SGC7901 cell lines and normal gastric epithelial cell line GES-1. EdU and colony formation assay were performed to confirm the cytotoxic effect of Sophoridine on AGS and SGC7901 cells. The apoptotic effects of Sophoridine on AGS and SGC7901 cells were measured by Flow cytometry. Transwell assay was used to evaluate the effects of Sophoridine on migration and invasion of AGS and SGC7901 cells. The protein expression of Sophoridine on AGS and SGC7901 cells were detected via Western blot. Results: We demonstrated that Sophoridine exerts potent tumor-suppressive activities, including inhibition of proliferation, colony formulation, migration and invasion, as well as induction of apoptosis of gastric cancer cells. In addition, we further showed that Sophoridine induces G2/M cell cycle arrest via inhibiting double-stranded DNA breaks repair and enhances the efficacy of cisplatin in gastric cancer cells. Molecular studies further revealed that Sophoridine depends on Estrogen-related receptor gamma (ESRRG) to perform tumor-suppressive activities and which leads to the degradation of β-catenin in an ubiquitin-proteasome pathway independent manner. Conclusions: Our study provided the promising preclinical anti-tumor evidence for the potential application of Sophoridine against gastric cancer.