目的 探讨雷公藤Tripterygium wilfordii抑制三阴性乳腺癌（triple-negative breast cancer，TNBC）增殖及骨转移的作用及机制。方法 通过MTT、细胞划痕、结晶紫染色及克隆形成实验，评估雷公藤对4T1细胞增殖、迁移及克隆形成的抑制作用；采用Western blotting分析雷公藤对4T1细胞铁死亡相关蛋白表达的影响。体内构建小鼠乳腺癌骨转移模型，利用活体成像、CT扫描及TRAP染色观察雷公藤对骨转移的干预作用。结果 雷公藤显著抑制4T1细胞的增殖、迁移和克隆形成（P＜0.05、0.01、0.001），同时诱导铁死亡并降低核因子E2相关因子2（nuclear factor E2-related factor 2，Nrf2）、溶质载体家族7成员11（solute carrier family 7 member 11，SLC7A11）、谷胱甘肽过氧化物酶4（glutathione peroxidase 4，GPX4）蛋白的表达（P＜0.05、0.01、0.001）。体内实验结果显示，雷公藤可抑制乳腺癌骨转移模型小鼠肿瘤的进展，降低继发性肺转移的发生；通过离体骨组织3D重建发现，雷公藤显著缓解了肿瘤诱导的骨质流失；TRAP染色证实雷公藤通过抑制破骨细胞过度分化和募集，阻断了肿瘤-破骨细胞的恶性循环，有效维持了胫骨和股骨的骨微结构完整性。结论 雷公藤体外可抑制TNBC细胞增殖，体内可有效干预TNBC骨转移，显示出其潜在的治疗价值。

Objective To investigate the effect and mechanism of Tripterygium wilfordii in inhibiting the proliferation and bone metastasis of triple-negative breast cancer (TNBC). Methods MTT assay, wound healing assay, crystal violet staining and colony formation assay were used to evaluate the inhibitory effect of T. wilfordii on proliferation, migration and colony formation of 4T1 cells; Western blotting was performed to examine the effect of T. wilfordii on expressions of ferroptosis-related proteins in 4T1 cells. An in vivo mouse model of breast cancer bone metastasis was constructed, and the effect of T. wilfordii on bone metastasis was observed using in vivo imaging, CT scans and TRAP staining. Results T. wilfordii significantly inhibited the proliferation, migration and colony formation of 4T1 cells (P < 0.05, 0.01, 0.001), induced ferroptosis and down-regulated the expressions of nuclear factor E2-related factor 2 (Nrf2), solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4) proteins (P < 0.05, 0.01, 0.001). In vivo experiment results showed that T. wilfordii could inhibit the progression of tumor in bone metastasis model mice of breast cancer and reduce the occurrence of secondary lung metastasis; T. wilfordii significantly alleviated tumor-induced bone loss through 3D reconstruction of ex vivo bone tissue; TRAP staining confirmed that T. wilfordii inhibited excessive osteoclast differentiation and recruitment, blocking the malignant cycle between tumors and osteoclasts, and effectively maintained the structural integrity of the tibial and femoral bone microstructures. Conclusion In vitro, T. wilfordii inhibits the proliferation of TNBC cells and promotes osteoblastic mineralization. In vivo, it effectively interferes with TNBC bone metastasis, demonstrating its potential therapeutic value.

R285.5

泰山学者青年专家计划项目（tsqn202211136）；山东省中医药科技项目（M-2023182）；国家自然科学基金资助项目（21775061）；济南市“新高校20条”资助项目（202228085）；山东中医药大学青年创新团队支持计划项目（22202401）