胆囊癌（GBC）是胆管系统中最具有侵袭性的恶性肿瘤。 GBC患者的预后极差。 熟地黄醇是从传统中药丹参中提取和纯化的二萜化合物，在多种肿瘤中显示出具有前景的抗癌作用。 然而，熟地黄醇在GBC中尚未得到研究。采用CCK-8、集落形成试验和EdU-488 DNA合成试验，研究了熟地黄醇对GBC细胞增殖的影响。 细胞侵袭和迁移试验和划痕愈合试验用于探索熟地黄醇对GBC细胞侵袭和迁移能力的影响。采用mRNA-seq探索潜在机制。西方印迹和免疫组织化学染色用于检测蛋白质水平。 CHIP和双荧光素酶检测用于验证结合模体。采用GBC裸鼠模型评估熟地黄醇的抗肿瘤效果和安全性。在体外熟地黄醇抑制了GBC细胞的增殖和侵入和迁移。 此外，熟地黄醇通过下调MAGEB2的表达发挥抗肿瘤作用。 在机械上，熟地黄醇上调FOXO4表达，并促进其在核内积累以抑制MAGEB2的转录。此外，熟地黄醇在GBC裸鼠模型中抑制了肿瘤生长，安全性良好。熟地黄醇可能是治疗GBC的一种有前途的药物，具有有效性和安全性。 版权所有©2023年作者。 由Elsevier GmbH出版。保留所有权利。

Gallbladder cancer (GBC) is the most aggressively malignant tumor in the bile duct system. The prognosis for patients with GBC is extremely poor. Ponicidin is a diterpenoid compound extracted and purified from the traditional Chinese herb Rabdosia rubescens, and showed promising anti-cancer effects in a variety of tumors. However, Ponicidin has not been investigated in GBC.CCK-8, colony formation assay and EdU-488 DNA synthesis assay were performed to investigate the effect of Ponicidin on GBC cells proliferation. Cell invasion and migration assays and wound-healing assay were used to explore the effect of Ponicidin on invasion and migration ability of GBC cells. mRNA-seq was adopted to explore the underlying mechanisms. Western blot and immunohistochemical staining were conducted to detect the protein level. CHIP assay and dual-luciferase assay were used to validate binding motif. Nude mouse model of GBC was used to assess the anti-tumor effect and safety of Ponicidin.Ponicidin inhibited the proliferation and cell invasion and migration of GBC cells in vitro. Moreover, Ponicidin exerted anti-tumor effects by down-regulating the expression of MAGEB2. Mechanically, Ponicidin upregulated the FOXO4 expression and promoted it to accumulate in nucleus to inhibit the transcript of MAGEB2. Furthermore, Ponicidin suppressed tumor growth in the nude mouse model of GBC with excellent safety.Ponicidin may be a promising agent for the treatment of GBC effectively and safely.Copyright © 2023 The Author(s). Published by Elsevier GmbH.. All rights reserved.