结直肠癌（CRC）是癌症相关死亡的第二大常见原因，其特点是具有广泛的侵袭性和转移性。先前的研究表明，从圆叶牡荆果实中提取的牡荆素可以阻止肿瘤进展。然而，涉及CRC治疗的分子机制尚未完全确定。我们的研究旨在探讨牡荆卡平在CRC中的抗癌活性、靶点和分子机制，希望为CRC患者提供新的治疗方法。通过各种实验进行评估，包括 MTT、克隆形成、EDU、细胞周期和细胞凋亡测定以及肿瘤异种移植模型。 CETSA、无标记定量蛋白质组学和 Biacore 用于鉴定牡荆卡平靶标。采用WB、Co-IP、泛素化实验、IF、分子对接、MST和细胞转染等方法研究牡荆卡平在CRC细胞中的作用机制。此外，我们分析了 TCGA 和 GEPIA 数据集以及临床样本中靶蛋白的表达模式和相关性。最后，通过伤口愈合、Transwell、尾静脉注射模型和组织切片染色来证明牡荆卡平在体外和体内对结直肠癌的抗转移作用。我们的研究结果表明，牡荆卡平通过直接与肌苷单磷酸脱氢酶2结合而表现出抗癌活性（ IMPDH2)，并且它通过破坏 IMPDH2 和 c-Myc 之间的相互作用来促进 c-Myc 泛素化，从而抑制上皮间质转化 (EMT)。 Vitexicarpin 通过在体外和体内逆转 EMT 来阻碍 CRC 细胞的迁移和侵袭。此外，这些结果通过CRC细胞中IMPDH2的过表达和敲低得到验证。这些结果表明，牡荆卡平调节IMPDH2和c-Myc之间的相互作用，从而在体外和体内抑制CRC增殖和转移。这些发现为 CRC 治疗引入了潜在的分子靶标，并揭示了肿瘤中 c-Myc 调节的新机制。版权所有 © 2024。由 Elsevier GmbH 出版。

Colorectal cancer (CRC) is the second most common cause of cancer-related mortality and is characterised by extensive invasive and metastatic potential. Previous studies have shown that vitexicarpin extracted from the fruits of Vitex rotundifolia can impede tumour progression. However, the molecular mechanisms involved in CRC treatment are still not fully established.Our study aimed to investigate the anticancer activity, targets, and molecular mechanisms of vitexicarpin in CRC hoping to provide novel therapies for patients with CRC.The impact of vitexicarpin on CRC was assessed through various experiments including MTT, clone formation, EDU, cell cycle, and apoptosis assays, as well as a tumour xenograft model. CETSA, label-free quantitative proteomics, and Biacore were used to identify the vitexicarpin targets. WB, Co-IP, Ubiquitination assay, IF, molecular docking, MST, and cell transfection were used to investigate the mechanism of action of vitexicarpin in CRC cells. Furthermore, we analysed the expression patterns and correlation of target proteins in TCGA and GEPIA datasets and clinical samples. Finally, wound healing, Transwell, tail vein injection model, and tissue section staining were used to demonstrate the antimetastatic effect of vitexicarpin on CRC in vitro and in vivo.Our findings demonstrated that vitexicarpin exhibits anticancer activity by directly binding to inosine monophosphate dehydrogenase 2 (IMPDH2) and that it promotes c-Myc ubiquitination by disrupting the interaction between IMPDH2 and c-Myc, leading to epithelial-mesenchymal transition (EMT) inhibition. Vitexicarpin hinders the migration and invasion of CRC cells by reversing EMT both in vitro and in vivo. Additionally, these results were validated by the overexpression and knockdown of IMPDH2 in CRC cells.These results demonstrated that vitexicarpin regulates the interaction between IMPDH2 and c-Myc to inhibit CRC proliferation and metastasis both in vitro and in vivo. These discoveries introduce potential molecular targets for CRC treatment and shed light on new mechanisms for c-Myc regulation in tumours.Copyright © 2024. Published by Elsevier GmbH.