β‐catenin inhibitor ICG‐001 suppress cell cycle progression and induce autophagy in endometrial cancer cells

Abstract

AbstractThe incidence of endometrial cancer has been rising in recent years. Gene mutation and high protein expression of β‐catenin are commonly detected in endometrioid endometrial cancer. ICG‐001 is a β‐catenin inhibitor via blocking the complex formation of β‐catenin and cAMP response element‐binding protein (CREB)‐binding protein (CBP). This study aims to investigate the effect of ICG‐001 on endometrial cancer inhibition. First, endometrial carcinoma patient‐derived xenograft (PDX)‐derived organoids and primary cells were used to verify the inhibiting ability of ICG‐001 on endometrial cancer. Furthermore, endometrial cancer cell lines were used to investigate the anticancer mechanism of ICG‐001. Using MTT assay and tumor spheroid formation assay, ICG‐001 significantly reduced the cell viability of HEC‐59 and HEC‐1A cells. ICG‐001 enhanced cisplatin‐mediated cytotoxicity. ICG‐001 decreased cancer stem cell sphere formation. ICG‐001 decreased the protein expressions of CD44, hexokinase 2 (HK2), and cyclin A. ICG‐001 lowered the cell cycle progression by flow cytometer analysis. Autophagy, but no apoptosis, was activated by ICG‐001 in endometrial cancer cells. Autophagy inhibition by ATG5 silencing enhanced ICG‐001‐mediated suppression of cell viability, tumor spheroid formation, and protein expression of cyclin A and CD44. This study clarified the mechanism and revealed the clinical potential of ICG‐001 against endometrial cancer.