Regulatory Effect of Huadu Sanyinfang on PI3K/Akt/NF-κB Pathway in Triple-negative Breast Cancer Patients with Qi-deficiency Constitution： An Exploration Based on Differential Expression of miRNA / 中国实验方剂学杂志

ABSTRACT

Objective:To explore the regulatory effect of Huadu Sanyinfang on phosphatidylinositol 3 kinase（PI3K）/protein kinase B（Akt）/transcription factor nuclear factor-<italic>κ</italic>B （NF-<italic>κ</italic>B） in triple-negative breast cancer （TNBC） patients with qi-deficiency constitution based on the differential expression of miRNA. Method:Based on previous research results， this study conducted the bioinformatics analysis to predict the target genes responsible for regulating the differential expression of miRNA between patients with qi-deficiency constitution and those with moderate constitution， which were intersected with TNBC target genes. The resulting intersection targets were then subjected to Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis and protein-protein interaction （PPI） network analysis to obtain the key pathways and target genes for differentially expressed miRNA in regulating TNBC. TNBC patients with Qi-deficiency constitution were treated with Huadu Sanyinfang for three years after they completed the standard Western medical treatment. The peripheral blood of the patients was sampled before and after medication for detecting gene expression in the key pathways. Result:The comparison between patients with Qi-deficiency constitution and those with moderate constitution revealed 49 differentially expressed miRNAs （16 up-regulated and 33 down-regulated）， which regulated 1 445 TNBC target genes. As demonstrated by PPI and KEGG pathway enrichment analysis， the key genes were mainly tumor protein p53 （TP53）， Akt1， epidermal growth factor receptor （EGFR）， mitogen-activated protein kinase 3 （MAPK3）， vascular endothelial growth factor A （VEGRA）， and tumor necrosis factor （TNF）. The key pathways included PI3K/Akt， MAPK， and RAS signaling pathways. A total of 11 TNBC patients with qi-deficiency constitution were enrolled. Compared with the situations before treatment， the expression levels of p105 subunit of NF-κB （NF-<italic>κ</italic>B1） and Akt1 in the PI3K/Akt signaling pathway were down-regulated after medication， while the levels of catalytic subunit alpha of PI3K （PIK3CA） and B-cell lymphoma-xL （Bcl-xL） were up-regulated. The differences in NF-<italic>κ</italic>B1 and Akt1 expression were statistically significant. Conclusion:Huadu Sanyinfang is able to affect the gene expression of PI3K/Akt/NF-<italic>κ</italic>B signaling pathway in TNBC patients with Qi-deficiency constitution. Specifically， it down-regulates NF-<italic>κ</italic>B1 and Akt1 expression and up-regulates PIK3CA and Bcl-xL.