Targeting APC/CCDC20 by Pro-TAME Suppresses Tumor Proliferation and Induces Apoptosis in Endometrial Carcinoma

Abstract

Background: Anaphase-promoting complex/cyclosome (APC/C) is a multi-subunit E3 ubiquitin ligase that recruits substrates for ubiquitination and subsequent degradation. As one of the two co-activators of APC/C, cell division cycle protein 20 (CDC20) plays a crucial role in cell cycle regulation. The objective of our study was to explore the therapeutic potential of targeting APC/CCDC20 in endometrial carcinoma (EC). Methods: We performed comprehensive bioinformatics analysis to screen novel targets for EC treatment. The expression of CDC20 in normal endometrial and EC tissues was analyzed by immunohistochemistry. We treated EC cells with varying concentrations of APC/C inhibitors and evaluated their effects on cell proliferation and apoptosis using Cell Counting Kit-8 (CCK-8) assay and flow cytometry analysis. We performed wound healing and transwell assays to evaluate the migration ability of EC cell lines. Results: CDC20 was identified as a potential therapeutic target for EC. We found that the expression level of CDC20 in EC tissue is significantly higher than in nonmalignant tissue. Treatment with pro-Tosyl-L-Arginine Methyl Ester (TAME) inhibited the proliferation of EC cells in a time- and dose-dependent pattern. High concentrations of pro-TAME induced apoptosis in EC cells. Furthermore, the inhibitory effects of pro-TAME on EC cells were amplified by the co-addition of Apcin at low concentrations. However, treatment with pro-TAME did not affect the migratory ability of EC cells. Conclusions: Our findings suggest that the inhibition of APC/CCDC20 by pro-TAME, in combination with Apcin, may represent a promising approach for the treatment of EC that warrants further investigation.

Keywords

• endometrial carcinoma
• anaphase promoting complex/cyclosome
• cdc20
• pro-tame