Sancao decoction combined with cisplatin alleviates lung metastasis of breast cancer via relieving immune suppression in the pre-metastatic niche  

Sancao decoction combined with cisplatin alleviates lung metastasis of breast cancer via relieving immune suppression in the pre-metastatic

作　　者：Shi-Ying Zhang Jia-Cheng Guo Hui-Ling Jiang Ya-Nan Li Yu-Juan Wang Xin-Yan Dai Li-Du Shen Xiao-Bi Adu Li-Kai Pu Heng-Xiu Yan 

机构地区：[1]College of Grassland Resources,Southwest Minzu University,Chengdu 610225,China [2]College of Pharmacy and Food,Southwest Minzu University,Chengdu 610225,China.

出　　处：《Integrative Medicine Discovery》2025年第2期1-10,共10页

基　　金：supported by Fundamental Research Funds for the Central Universities(ZYN2024075);Chengdu Science and Technology Bureau Technology Innovation R&D Project(2024-YF05-02236-SN);the Applied Basic Research Project of the Sichuan Science Technology Department(2021YJ0256).Peer review information。

摘　　要：Background:The traditional Chinese medicine compound Sancao decoction(SCD)is a folk prescription for regulating immunity.It is composed of 8 Chinese herbal medicines,such as Prunellae Spica(Xiakucao),Houttuyniae Herba(Yuxingcao),Lysimachiae Herba(Jinqiancao)and so on.In cancer,the interleukin-6(IL-6)/the signal transducer and the activator of transcription 3(STAT3)pathway directly promotes the proliferation,survival and angiogenesis of cancer cells,and arginase-1(ARG-1)is a key enzyme for myeloid-derived suppressor cells(MDSCs)to exert immunosuppressive function.It is not clear whether SCD regulates the expression of ARG-1 in MDSCs through the IL-6/STAT3 pathway.Therefore,we explored the effect and mechanism of SCD on lung metastasis of breast cancer.Methods:The components in SCD have been analyzed by HPLC-MS.A spontaneous metastasis model of breast cancer was established by injecting 4T1 cells into the mammary fat pad of BALB/c mice.Pre-metastatic niche(PMN)formation and the role of SCD on PMN were evaluated by lung metastasis nodules,lung pathology tests and immunofluorescence for 2–4 weeks.Serum tests and hematoxylin-eosin staining(H&E)were used to evaluate the side effects of cisplatin.Western blot and ELISA were used to detect proteins and cytokines of the STAT3 signaling pathway in mouse lung tissue.Results:Compared with SCD or cisplatin treatment alone,SCD/cisplatin(CP)synergistic administration not only significantly inhibited orthotropic breast tumor growth,but also reduced lung metastasis and alleviated the hepatorenal toxicity induced by CP in vivo.Remarkably,the combination effectively inhibited PMN formation and the accumulation of MDSCs in the lung PMN,accompanied by the significant infiltration of CD4+T and CD8+T-lymphocytes in the lung PMN and spleen.In addition,the SCD/CP combination downregulated protein expression levels of STAT3,p-STAT3,IL-6 and ARG-1 in the lung PMN of breast cancer mice.Conclusion:The synergistic effect of SCD and cisplatin inhibited MDSCs aggregation and the immunosuppres

关 键 词：pre-metastatic niche breast cancer lung metastasis MDSCS Sancao decoction 

分 类 号：R73[医药卫生—肿瘤]