EZH2是一个高度保守的组蛋白甲基转移酶，在肿瘤发生和发展中起着重要作用。EZH2的抑制剂tazemetostat已被批准用于治疗转移性或局部晚期上皮样肉瘤和复发或难治性滤泡性淋巴瘤。然而，tazemetostat在食管癌中单独使用或与其他药物联合使用的效果尚未报告。在本研究中，我们通过转录组学和蛋白质组学分析发现EZH2在食管癌中的mRNA和蛋白水平均高度表达。此外，CCK8、集落形成、细胞周期和细胞凋亡实验的结果显示，tazemetostat对食管癌细胞具有抗肿瘤作用。机理上，tazemetostat处理的细胞和对照组的RNA测序分析表明，tazemetostat主要抑制c-Myc信号通路及其靶点，这一结果经过了免疫印迹验证。JQ-1，一种抑制剂，已被证明可以减弱肿瘤中的c-Myc信号传导。因此，以tazemetostat为基础的与JQ-1结合的治疗策略是有前景的。结果表明，tazemetostat和JQ-1在体外和体内对食管癌具有协同作用。© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

EZH2, a highly conserved histone methyltransferase, plays an essential role in tumorigenesis and development. The inhibitor of EZH2 tazemetostat has been approved to treat metastatic or locally advanced epithelioid sarcoma and recurrent or refractory follicular lymphoma. However, the effect of tazemetostat alone or in combination with other drugs in esophageal cancer has not been reported. In this study, we found that EZH2 was highly expressed in esophageal cancer at both mRNA and protein levels through transcriptomic and proteomic analyses. Furthermore, the results of CCK8, colony formation, cell cycle and cell apoptosis assays revealed that tazemetostat exerted an antitumour effect on esophageal cancer cells. Mechanistically, RNA-sequencing analysis of the tazemetostat-treated cells and vehicle-treated ones suggested that tazemetostat mainly inhibited the c-Myc signaling pathway and its targets, which was validated by western blotting. JQ-1, an inhibitor of bromodomain 4, was proven to attenuate c-Myc signaling in tumors. Thus, a therapeutic strategy based on tazemetostat in combination with JQ-1 is promising. The results demonstrated that tazemetostat and JQ-1 had a synergistic effect in vitro and in vivo for esophageal cancer.© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.