肝细胞癌（HCC）是全球健康问题之一。乙型肝炎病毒（HBV）是肝癌的主要原因之一。 HCC 患者临床结果不佳归因于一小群被称为癌症干细胞 (CSC) 的癌细胞。在这项工作中，我们研究了使用 tazemetostat (Taz) 抑制 zeste 同源物 2 (EZH2) 增强子的效果，zeste 同源物 2 是一种已知在 CSC 中过度表达的组蛋白甲基转移酶。在 HCC 细胞系 (HEPG2) 和乙型肝炎病毒转染的 HEPG2 (HBV/HEPG2) 细胞中评估了 Taz 的作用。 MTT 测定显示，用 0.5、1、4 或 6 μM Taz 处理 48 小时后，HEPG2 细胞活力显着下降。 HEPG2 和 HBV/HEPG2 细胞与 0.5 或 1 μM Taz 孵育 48 小时，然后收集细胞和上清液，使用酶对 EZH2、CD13、上皮细胞粘附分子 (EpCAM) 和 β-catenin 进行蛋白表达分析连锁免疫吸附测定（ELISA）。 Taz 对 HEPG2 和 HBV/HEPG2 细胞中的 EZH2、CD13 和 β-catenin 显示出显着的剂量依赖性抑制作用。此外，EpCAM 蛋白水平在 HBV/HEPG2 中显着降低，但在单独的 HEPG2 细胞系中则没有。我们的结果表明，Taz 抑制 EZH2 会导致 β-catenin 信号传导下调，并最终降低 CD13 和 EpCAM 的表达，这是 CSC 的特征。目前的研究表明，Taz 可能是治疗 HCC（包括 HBV 诱导的 HCC）的一种有前途的治疗方法，可与放疗/化疗联合使用以靶向 CSC 并预防肿瘤复发。© 2023。作者。

Hepatocellular carcinoma (HCC) is one of the global health concerns. Hepatitis B virus (HBV) is one of the major causes of HCC. Poor clinical outcome of HCC patients is attributed to a small population of cancer cells known as cancer stem cells (CSCs). In this work, we studied the effect of inhibiting the enhancer of zeste homologue 2 (EZH2), a histone methyltransferase known to be overexpressed in CSCs, using tazemetostat (Taz). The effect of Taz was assessed in the HCC cell line (HEPG2) and Hepatitis B virus-transfected HEPG2 (HBV/HEPG2) cells. MTT assay showed a significant decrease in HEPG2 cells viability after 48 h treatment with either 0.5, 1, 4 or 6 μM Taz. HEPG2 and HBV/HEPG2 cells were incubated with either 0.5 or 1 μM Taz for 48 h, and then, the cells and supernatants were collected for protein expression analysis of EZH2, CD13, epithelial cell adhesion molecule (EpCAM) and β-catenin using enzyme-linked immunosorbent assay (ELISA). Taz showed a significant dose-dependent inhibition of EZH2, CD13 and β-catenin in HEPG2 and HBV/HEPG2 cells. Also, EpCAM protein levels were significantly decreased in HBV/HEPG2 but not in HEPG2 cell line alone. Our results indicate that Taz inhibition of EZH2 leads to downregulation of β-catenin signaling and eventually decreased expression of CD13 and EpCAM, which are characteristic for CSCs. The present study suggests that Taz could be a promising treatment for HCC including HBV-induced HCC that might be used in combination with radio/chemotherapy to target CSCs and prevent tumor relapse.© 2023. The Author(s).