JPTQ Decoction Inhibits Tumor Proliferation and Lung Metastasis in Tumor-bearing Mice with Triple Negative Breast Cancer

Background: With the increasing incidence of breast cancer and the integration of multiple methods in the treatment, traditional Chinese medicine plays an increasingly important role in the comprehensive treatment of breast cancer. we aimed to determine the anti-cancer metastasis effect of Jianpi Tiaoqi Decoction (JPTQ) on breast cancer-bearing mice by monitoring the effects of its on tumor proliferation, apoptosis, angiogenesis, epithelial to mesenchymal transition (EMT) process and regulation of immune microenvironment. Methods. The general phenotype of the Cancer-bearing mice was monitored. Bioluminescence-imaging was performed to assess the tumor status and the metastatic status of other organs. We investigated its mechanism of the effect through transcriptome analysis, Flow Cytometry(FCM) was used to analyze peripheralblood CD4 + T cells, spleen T helper 1 (Th1) cell, the proportion of MDSCs in lung. The changes of EMT process, vascular endothelial growth factor (VEGF) and Ki-67, Caspase-3 and Bcl-2 were detected by quantitative real time polymerase chain reaction (q-PCR), western blot (WB) or immunohistochemistry (IHC). Results. JPTQ inhibited the tumors proliferation and reduced lung metastasis. The transcriptome analysis of lung and tumor tissues indicated that EMT-related genes, angiogenesis, proliferation and apoptosis genes were regulated in JPTQ group, and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis observed enrichment of immune-related pathways. FCM suggested that JPTQ could reduced the proportion of M-MDSCs in the lung, and increased peripheral blood CD4 + T cells and Th1 cells in spleen. The q-PCR, WB or IHC assay demonstrated that E-cadherin was up-regulated in lung and tumor tissue, and Snail was down-regulated, the expression of matrix metalloprotein-9(MMP-9)was down-regulated in lung tissue. IHC showed the down-regulation of Ki67 and VEGF in lung and tumo tissues. WB found that Cleved-Caspase3 was significantly up-regulated, while Bcl-2 was down-regulated. Conclution. JPTQ can inhibit proliferation, angiogenesis, promote apoptosis and improve the immune microenvironment, and reverse the EMT process to inhibit the proliferation and metastasis of TNBC.