ABSTRACT
Traditional Chinese medicine, specifically the Jianpi Tiaoqi (JPTQ) decoction, has been explored for its role in treating breast cancer, particularly in inhibiting lung metastasis in affected mice. Our study evaluated the effects of JPTQ on several factors, including tumour growth, apoptosis, angiogenesis, epithelial-to-mesenchymal transition (EMT) and immune microenvironment regulation. We used bioluminescence imaging to observe in situ tumour growth and potential lung metastasis. Transcriptomic analysis provided insights into gene expression, whereas flow cytometry was used to examine changes in specific immune cells, such as CD4+ T cells and myeloid-derived suppressor cells. Several essential proteins and genes, including vascular endothelial growth factor (VEGF), matrix metalloprotein-9 (MMP-9) and B-cell lymphoma 2 (Bcl-2), were assessed through quantitative real-time polymerase chain reaction, western blotting and immunohistochemistry. Our findings showed that JPTQ treatment inhibited tumour proliferation in cancer-bearing mice. Bioluminescence imaging and pathological analysis indicated a reduction in lung metastasis. Transcriptome analysis of lung and tumour tissues indicated that the genes associated with EMT, angiogenesis, proliferation and apoptosis were regulated in the JPTQ-treated group. Kyoto Encyclopedia of Genes and Genomes analysis suggested enrichment of immune-related pathways. Flow cytometry indicated that JPTQ treatment reduced the proportion of monocyte-myeloid-derived suppressor cells in the lung and increased the number of CD4+ T cells in the peripheral blood and the number of T helper 1 (Th1) cells in the spleen (P < 0.05). E-cadherin and cleaved caspase 3 were upregulated, whereas Snail, Bcl-2, Ki67 and VEGF were downregulated in the lung and tumour tissues; moreover, the expression of MMP-9 was downregulated in the lung tissue (P < 0.05). In essence, JPTQ not only inhibits tumour growth in affected mice, but also promotes positive immune responses, reduces angiogenesis, boosts tumour cell apoptosis, reverses EMT and decreases breast cancer lung metastasis.
Subject(s)
Cell Proliferation , Drugs, Chinese Herbal , Epithelial-Mesenchymal Transition , Lung Neoplasms , Triple Negative Breast Neoplasms , Animals , Lung Neoplasms/pathology , Lung Neoplasms/drug therapy , Lung Neoplasms/secondary , Lung Neoplasms/metabolism , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/therapeutic use , Mice , Cell Proliferation/drug effects , Female , Triple Negative Breast Neoplasms/pathology , Triple Negative Breast Neoplasms/drug therapy , Epithelial-Mesenchymal Transition/drug effects , Cell Line, Tumor , Apoptosis/drug effects , Gene Expression Regulation, Neoplastic/drug effects , Tumor Microenvironment/drug effects , Neovascularization, Pathologic/drug therapy , Neovascularization, Pathologic/pathologyABSTRACT
In this paper, the production of rhamsan gum from Sphingomonas sp. CGMCC 6833 at different pH values was investigated. Based on kinetic analysis, a two-stage strategy for pH control was proposed. During the first 10 h, pH was controlled at 7.5 to maintain high specific cell growth rate and specific glucose consumption rate. After 10 h, pH decreased naturally to 7.0; this value was retained to maintain high specific rhamsan gum formation rate. Using this method, the maximum concentration and productivity of rhamsan gum reached 18.56 ± 1.68 g/L and 0.290 ± 0.026 g/L/h, which are 12.83 and 12.84 % higher than the optimum results obtained at natural pH, respectively.
