结直肠癌（CRC）在全球死亡率中排名第二，需要有效且负担得起的治疗方法。环维黄杨星D（CVB-D）是经批准的传统成药黄杨宁片的主要有效成分，主要用于心血管治疗。作为一种具有多种生物活性的天然化合物，CVB-D 具有潜在的抗癌活性。在人类 CRC 系中测定了细胞活力和克隆形成能力。利用蛋白质印迹、免疫荧光测定、透射电子显微镜和衰老相关β-半乳糖苷酶（SA-β-Gal）染色来研究细胞自噬和衰老。通过虚拟预测和实验验证来探索分子机制。采用患者来源的异种移植物（PDX）、葡聚糖硫酸钠盐（DSS）和偶氮甲烷（AOM）/DSS小鼠模型进行体内研究。CVB-D通过诱导自噬和抑制晚期CRC细胞/小鼠的生长和发育。通过含有 TCP1 亚基 3 (CCT3)/yes 相关蛋白 (YAP) 轴的伴侣蛋白来抑制衰老活动。 CVB-D 通过与 CCT3 的 ATP 位点相互作用，成为一种有前景的 CCT3 抑制剂。在 PDX 肿瘤中，CVB-D 通过靶向 CCT3 显示出潜在的治疗效果。 CVB-D 治疗减轻了 DSS 诱导的小鼠结肠炎模型，并通过其对 CCT3 的作用减弱了 AOM/DSS 诱导的腺瘤性息肉形成。我们的研究为 CVB-D 可能被认为是一种治疗方法提供了科学依据。用于治疗 CRC 患者的潜在候选药物。© 2024 英国药理学会。

Colorectal cancer (CRC) ranks second in mortality worldwide and requires effective and affordable remedies. Cyclovirobuxine D (CVB-D) is the main effective component of Huangyangning tablet, an approved traditional patent medicine, which is mainly used for cardiovascular treatment. As a multibioactive natural compound, CVB-D possesses underlying anticancer activities.Cell viability and clone-forming ability were determined in human CRC lines. Western blot, immunofluorescence assay, transmission electron microscopy and senescence-associated β-galactosidase (SA-β-Gal) staining were utilized to investigate cell autophagy and senescence. The molecular mechanisms were explored by virtual prediction and experimental validation. Patient-derived xenograft (PDX), dextran sulfate sodium salt (DSS), and azomethane (AOM)/DSS mouse models were employed for in vivo studies.CVB-D inhibited the growth and development of advanced CRC cells / mice by inducing autophagic and senescent activities through the chaperonin containing TCP1 subunit 3 (CCT3)/yes-associated protein (YAP) axis. CVB-D acted as a promising inhibitor of CCT3 by interacting with its ATP site. In PDX tumours, CVB-D showed potential therapeutic effects by targeting CCT3. Treatment with CVB-D alleviated the mouse model of colitis induced by DSS and attenuated AOM/DSS-induced formation of adenomatous polyps by its action on CCT3.Our study has provided a scientific basis for the suggestion that CVB-D may be recognized as a prospective drug candidate for the therapy of CRC in patients.© 2024 British Pharmacological Society.