近年来，子宫内膜癌的发病率逐渐上升。基因突变和β-连环蛋白的高蛋白表达在子宫内膜癌中普遍存在。ICG-001是一种β-连环蛋白抑制剂，通过阻断β-连环蛋白和cAMP 反应元件结合蛋白结合蛋白复合物的形成。本研究旨在调查ICG-001对抑制子宫内膜癌的影响。首先，使用子宫内膜癌患者来源的异种移植物（PDX）衍生的器官样以及原代细胞来验证ICG-001对子宫内膜癌的抑制能力。此外，使用子宫内膜癌细胞系研究ICG-001的抗癌机制。通过MTT实验和肿瘤球形成实验，ICG-001显著降低了HEC-59和HEC-1A细胞的细胞存活率。ICG-001增强了顺铂的细胞毒作用。ICG-001降低了癌干细胞球形成。ICG-001降低了CD44、己糖激酶2（HK2）和细胞核蛋白A的蛋白表达。ICG-001通过流式细胞术分析降低了细胞周期进程。ICG-001在子宫内膜癌细胞中激活了自噬作用，而没有激活凋亡。通过ATG5沉默抑制自噬增强了ICG-001对细胞存活率、肿瘤球形成以及CD44和细胞核蛋白A的蛋白表达的抑制作用。本研究阐明了ICG-001的作用机制，并揭示了其对治疗子宫内膜癌具有的临床潜力。© 2023 Wiley Periodicals LLC.

The 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.© 2023 Wiley Periodicals LLC.