Yan Liping, Tan Qixing, Zhu Jia, He Yongfei, Tao Peng, He Jianxin
Department of Breast Surgery, Jiangxi Maternal and Child Health Hospital, Nanchang, PR China; Key Laboratory of High Incidence Tumor Prevention and Treatment Guangxi Medical University, Nanning, PR China.
Department of Breast Surgery, Guangxi Medical University Cancer Hospital, Nanning, PR China.
Biochem Pharmacol. 2025 Nov;241:117128. doi: 10.1016/j.bcp.2025.117128. Epub 2025 Jul 12.
Breast cancer liver metastasis presents a significant clinical challenge, requiring a deeper understanding of its underlying mechanisms. In this study, we explored the role of serum metabolites and gut microbiota in breast cancer liver metastasis, with a particular focus on the effects of glycochenodeoxycholic acid sodium salt (GCDC). Serum metabolites were analyzed using liquid chromatography-mass spectrometry (LC-MS), while gut microbiota composition was assessed through 16S rDNA sequencing of stool samples. Statistical analyses revealed a strong correlation between gut microbiota and GCDC levels, which varied markedly among breast cancer, breast cancer liver metastasis, and healthy control groups. GCDC was identified as a microbiota-related metabolite through high-throughput bioinformatics screening. In vitro experiments showed that GCDC inhibited breast cancer cell proliferation, migration, and invasion while inducing cell death. In vivo, GCDC treatment reduced subcutaneous tumor growth and prevented liver metastases, as evidenced by decreased Ki67 expression in tumor tissues. These findings suggested that GCDC suppresses breast cancer liver metastasis by inhibiting cancer cell growth and migration, underscoring its potential as a biomarker for early detection and a therapeutic agent for liver metastasis in patients with breast cancer. Further research is needed to clarify its mechanisms and explore its clinical applications.
乳腺癌肝转移带来了重大的临床挑战,需要对其潜在机制有更深入的了解。在本研究中,我们探讨了血清代谢物和肠道微生物群在乳腺癌肝转移中的作用,特别关注甘氨鹅去氧胆酸钠盐(GCDC)的影响。使用液相色谱 - 质谱联用(LC-MS)分析血清代谢物,通过对粪便样本进行16S rDNA测序评估肠道微生物群组成。统计分析显示肠道微生物群与GCDC水平之间存在强相关性,在乳腺癌、乳腺癌肝转移和健康对照组之间差异显著。通过高通量生物信息学筛选,GCDC被鉴定为一种与微生物群相关的代谢物。体外实验表明,GCDC抑制乳腺癌细胞的增殖、迁移和侵袭,同时诱导细胞死亡。在体内,GCDC治疗减少了皮下肿瘤生长并预防了肝转移,肿瘤组织中Ki67表达降低证明了这一点。这些发现表明,GCDC通过抑制癌细胞生长和迁移来抑制乳腺癌肝转移,突出了其作为早期检测生物标志物和乳腺癌肝转移患者治疗药物的潜力。需要进一步研究以阐明其机制并探索其临床应用。