| Citation: |
LI Xinyi, CUI Chuang, CHEN Wanqing, ZHU Weikang. Effect of Shugan Yishen Recipe on Microenvironment Gene Expression Profile and Immune-Related Gene Expression in Lung Metastasis of Breast Cancer[J]. Journal of Nanjing University of traditional Chinese Medicine, 2025, 41(3): 352-362. DOI: 10.14148/j.issn.1672-0482.2025.0352
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To investigate the mechanism of inhibition of breast cancer lung metastasis by Shugan Yishen Recipe by studying the effects of Shugan Yishen Recipe(SGYSR) on gene expression in the lung microenvironment of mice with breast cancer.
A high metastasis model of breast cancer was constructed, and the mice were randomly divided into saline group, low, medium, high(0.5, 1, 2 g ·kg-1) Shugan Yishen Recipe groups, and docetaxel group (5 mg ·kg-1), and intervened for 28 days. HE staining was used to observe the lung tissue structure; transcriptome analysis was performed on the metastatic foci, and the key differential gene expression was screened by bioinformatics analysis of the GO and KEGG pathway characteristics of the gene expression profiles, and the expression of key immune genes was analyzed by qPCR and Western blot. The expression of MDSCs was detected by flow cytometry; the expression of cytokines and chemokines including Cxcl2, and GM-CSF was detected by ELISA.
Compared with the saline group, the number of metastatic nodules in lung tissues of the middle and high dose groups of Shugan Yishen Recipe and docetaxel group were correspondingly lower; HE staining suggested that the degree of lung pathology was improved. There were 814 differentially expressed genes in the lung microenvironment of the high-dose group of Shugan Yishen Recipe and the saline group, of which 713 genes were down-regulated and 101 genes were up-regulated; screening for key inflammatory mediator genes in the Shugan Yishen Recipe group, Nfkbiz, Tnfaip3, Maff, Hspa1a, Hspb1 and Cxcl2, the inflammatory genes in the Shugan Yishen Recipe, as compared with that of the saline group, were significantly down-regulated (P < 0.05, P < 0.01), and ultimately its results were consistent with the trend of the transcriptome results. Western blot was used to verify the results at the protein level, and it was found that compared with the saline group, the protein expression levels of Nfkbiz, Tnfaip3, Maff, Hspa1a and Cxcl2 in the Shugan Yishen Recipe group were decreased(P < 0.05, P < 0.01), while the protein expression of Hspb1 was up-regulated(P < 0.01). Both the Shugan Yishen Recipe group and the docetaxel group could inhibit the expression of MDSCs (P < 0.001), and the expression of Cxcl2, and GM-CSF decreased to a certain extent (P < 0.05, P < 0.01).
Shugan Yishen Recipe can inhibit breast cancer lung metastasis and regulate the lung immune microenvironment genes in a wide range.
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