黄连碱 (COP) 已被证明具有广泛的抗癌特性，包括肝细胞癌 (HCC)。然而，COP治疗HCC的确切机制仍不清楚。本研究旨在探讨 COP 对抗 HCC 的潜在作用机制。通过评估COP在不同HCC细胞系和异种移植裸鼠中的抗HCC活性，发现COP在体外和体内均具有抑制HCC的作用。通过RNA-Seq分析，E2F7被确定为COP对抗HCC的潜在靶点，并且细胞周期被确定为可能的途径。 E2F7的过表达和CHK1的抑制表明COP通过下调E2F7和影响CHK1/CDC25A通路来抑制HCC的活性并诱导HCC细胞的G2/M期阻滞。最后，启动子片段化实验和染色质免疫沉淀显示COP通过抑制E2F4/NFYA/NFYB转录因子下调E2F7。总之，我们的研究表明，COP 通过影响关键转录因子下调 E2F7，从而诱导细胞周期停滞并抑制 HCC 细胞生长。这为 COP 在肿瘤治疗中的功效提供了进一步的证据。版权所有 © 2024。由 Elsevier B.V. 出版。

Coptisine (COP) has been shown to exhibit a wide range of anticancer properties, including in hepatocellular carcinoma (HCC). Nevertheless, the precise mechanism of COP in the treatment of HCC remains elusive. This study aims to investigate the potential mechanism of action of COP against HCC. By evaluating the anti-HCC activity of COP in different HCC cells lines and in xenografted nude mice, it was found that COP inhibited HCC in vitro and in vivo. Through RNA-Seq analysis, E2F7 was identified as a potential target of COP against HCC, as well as the cell cycle as a possible pathway. The overexpression of E2F7 and the inhibition of CHK1 demonstrated that COP inhibits the activity of HCC and induces G2/M phase arrest of HCC cells by down-regulating E2F7 and influencing the CHK1/CDC25A pathway. Finally, the promoter fragmentation experiments and chromatin immunoprecipitation revealed that COP down-regulated E2F7 by inhibiting the E2F4/NFYA/NFYB transcription factors. In conclusion, our study demonstrated that COP downregulates E2F7 by affecting key transcription factors, thereby inducing cell cycle arrest and inhibits HCC cell growth. This provides further evidence of the efficacy of COP in the treatment of tumors.Copyright © 2024. Published by Elsevier B.V.