Abstract The incidence of endometrial cancer (EC) is increasing globally, highlighting the need for novel therapies targeting molecular drivers of malignancy. The enhancer of zeste homolog 2 (EZH2), a histone methyltransferase implicated in tumor progression, is overexpressed in EC; however, its precise role and therapeutic potential remain unclear. This study investigated EZH2 expression and the efficacy of five EZH2 inhibitors (CPI-1205, EI1, EPZ005687, EPZ-6438, and GSK126) in eight EC cell lines, along with functional analyses of EZH2 knockdown. Western blotting and immunocytochemistry revealed variable EZH2 expression across EC cell lines, with high levels observed in HEC-50B and Ishikawa 3-H-12 cells. Drug sensitivity assays demonstrated that EZH2-high expressing cell lines were markedly more sensitive to EZH2 inhibitors, particularly GSK126, than EZH2-low expressing cell lines. siRNA-mediated EZH2 knockdown in HEC-50B cells led to reduced EZH2 expression and decreased sensitivity to EZH2 inhibitors, confirming target specificity and attenuation of cell proliferation, colony formation, migration, and invasion. These findings suggest that EZH2 plays a crucial role in promoting malignant phenotypes in EC, and that its expression level correlates with cell sensitivity to EZH2 inhibitors. Overall, EZH2 could serve as a valuable therapeutic target and predictive biomarker for personalized medicine in EC.
Onishi et al. (Tue,) studied this question.