肝细胞癌具有高度的血管侵袭和转移能力。血管样突触（VM）与肝细胞癌（HCC）的转移和复发密切相关。根据以往的研究，黄梅（Chloranthus henryi）具有抗肿瘤作用，但其在治疗肝细胞癌的分子机制尚未说明。本研究旨在研究黄梅提取物在HCC中的作用及其靶点和分子机制，以探索潜在的HCC治疗药物。在本研究中，我们从黄梅中分离出一种黄酮类化合物，化合物4，鉴定为黄檀酮A（FKA）。我们通过MTT法确定了FKA的抗HCC效果，并通过分子对接和CETSA鉴定了FKA的靶点。使用EDU、划痕愈合、转移、血管样突触和IF检测肝瘤细胞的增殖、迁移、侵袭和VM形成。采用WB、RT-PCR和细胞转染探究FKA对肝瘤细胞的机制。组织切片染色主要用于展示FKA对HCC的影响。我们证实FKA可以直接与CXCL12相互作用，并通过逆转EMT进程通过PI3K/Akt/NF-κB信号通路在体外和体内抑制了HCC的增殖、迁移、侵袭和VM形成。此外，通过过表达和沉默CXCL12，我们得到了相同的结果。FKA通过靶向CXCL12通过PI3K/Akt/HIF-1α/NF-κB/Twist1信号通路抑制HCC中的增殖、侵袭和转移，并逆转EMT。本研究提出FKA可能是HCC治疗的候选药物和前景策略。版权所有©2023 Elsevier GmbH发表。

Hepatocellular carcinoma has high ability of vascular invasion and metastasis. Vasculogenic mimicry (VM) is closely related to the metastasis and recurrence of hepatocellular carcinoma (HCC). According to previous research, Chloranthus henryi has anti-tumor effect, but its molecular mechanism in the treatment of HCC has not yet been stated.In our study, we aimed to investigate the effect of the extract of Chloranthus henryi in HCC and its target and molecular mechanism. We hoped to explore potential drugs for HCC treatment.In this study, we isolated a chalcone compound from Chloranthus henryi, compound 4, identified as flavokawain A (FKA). We determined the anti-HCC effect of FKA by MTT and identified the target of FKA by molecular docking and CETSA. Hepatoma cells proliferation, migration, invasion, and VM formation were examined using EDU, wound healing, transwell, vasculogenic mimicry, and IF. WB, RT-PCR, and cell transfection were used to explore the mechanism of FKA on hepatoma cells. Tissue section staining is mainly used to demonstrate the effect of FKA on HCC in vivo.We confirmed that FKA can directly interact with CXCL12 and HCC proliferation, migration, invasion, and VM formation were all inhibited through reversing the EMT progress in vitro and in vivo through the PI3K/Akt/NF-κB signaling pathway. Additionally, by overexpressing and knocking down CXCL12, we got the same results.FKA attenuated proliferation, invasion and metastatic and reversed EMT in HCC via PI3K/Akt/HIF-1α/NF-κB/Twist1 pathway by targeting CXCL12. This study proposed that FKA may be a candidate drug and prospective strategy for HCC therapy.Copyright © 2023. Published by Elsevier GmbH.