Institute of Traditional Chinese Medicine Surgery, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China.
Department of Breast Surgery, Shanxi Provincial Cancer Hospital, Taiyuan 030013, China.
Acta Biochim Biophys Sin (Shanghai). 2024 May 25;56(5):763-775. doi: 10.3724/abbs.2024015.
Traditional Chinese medicine (TCM) has been used to treat triple-negative breast cancer (TNBC), a breast cancer subtype with poor prognosis. Clinical studies have verified that the Sanyingfang formula (SYF), a TCM prescription, has obvious effects on inhibiting breast cancer recurrence and metastasis, prolonging patient survival, and reducing clinical symptoms. However, its active ingredients and molecular mechanisms are still unclear. In this study, the active ingredients of each herbal medicine composing SYF and their target proteins are obtained from the Traditional Chinese Medicine Systems Pharmacology database. Breast cancer-related genes are obtained from the GeneCards database. Major targets and pathways related to SYF treatment in breast cancer are identified by analyzing the above data. By conducting molecular docking analysis, we find that the active ingredients quercetin and luteolin bind well to the key targets KDR1, PPARG, SOD1, and VCAM1. experiments verify that SYF can reduce the proliferation, migration, and invasion ability of TNBC cells. Using a TNBC xenograft mouse model, we show that SYF could delay tumor growth and effectively inhibit the occurrence of breast cancer lung metastasis . PPARG, SOD1, KDR1, and VCAM1 are all regulated by SYF and may play important roles in SYF-mediated inhibition of TNBC recurrence and metastasis.
中医(TCM)已被用于治疗三阴性乳腺癌(TNBC),这是一种预后不良的乳腺癌亚型。临床研究已经证实,一种中药方剂三因方(SYF)对抑制乳腺癌复发和转移、延长患者生存时间和减轻临床症状有明显效果。然而,其活性成分和分子机制仍不清楚。在这项研究中,从中药系统药理学数据库中获得了组成 SYF 的每种草药的活性成分及其靶蛋白,从 GeneCards 数据库中获得了与乳腺癌相关的基因。通过分析上述数据,确定了与 SYF 治疗乳腺癌相关的主要靶点和途径。通过进行分子对接分析,我们发现活性成分槲皮素和木樨草素与关键靶点 KDR1、PPARG、SOD1 和 VCAM1 结合良好。实验验证了 SYF 可以降低 TNBC 细胞的增殖、迁移和侵袭能力。使用 TNBC 异种移植小鼠模型,我们表明 SYF 可以延缓肿瘤生长并有效抑制乳腺癌肺转移的发生。PPARG、SOD1、KDR1 和 VCAM1 均受 SYF 调节,可能在 SYF 介导的抑制 TNBC 复发和转移中发挥重要作用。