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.

Single-nucleus RNA sequencing and deep tissue proteomics reveal distinct tumour microenvironment in stage-I and II cervical cancer

“…The fourth subtype showed the marker genes of both dendritic cells (ADAM19, HDAC9, and MCOLN2) [52][53][54] and macrophages (SLC8A1, RUNX3, and LCP1) [55][56][57], which was referred to as C3-DC. The fifth subtype had several marker genes (SEMA3A, ESRRG , and IL18) [58][59][60] representing M1-like MΦ, which was labelled as C4-M1. The enrichment of biological processes (BPs) in each subtype was analysed (Fig.…”

Single-cell transcriptomics and deep tissue proteomics reveal distinct tumour microenvironment present in stage-I and II cervical cancer

“…The fourth subtype had the signatures of both dendritic cells (ADAM19, HDAC9, and MCOLN2)[48-50] and macrophages (SLC8A1, RUNX3, and LCP1) [51][52][53], which was referred to as C3-DC. The fth subtype had several marker genes (SEMA3A, ESRRG, and IL18) [54][55][56] representing M1-like MΦ, which was labelled as C4-M1. Although C3-DC and C4-M1 occupied the lowest proportions of the MΦ population in both groups, they had the highest number of maker genes, which were 108 and 250, respectively.…”