Utilizing network pharmacology to explore potential mechanisms of YiSui NongJian formula in treating myelodysplastic syndrome.

The study aims to explore potential mechanisms of YiSui NongJian formula (YSNJF) in treating myelodysplastic syndromes (MDS) by network pharmacology-based strategy. Active compounds and corresponding potential therapeutic targets of YSNJF were harvested by utilizing the database of TCMSP (Traditional Chinese Medicine Systems Pharmacology) and BATMAN-TCM (Bioinformatics Analysis Tool for Molecular mechanism of Traditional Chinese Medicine). MDS targets were adopted from GeneCard, KEGG (Kyoto Encyclopedia of Genes and Genomes), TTD (Therapeutic Target Database), DrugBank, and DisGeNet. Then a network of YSNJF- compounds-target-MDS network was harvested. The protein-protein interaction (PPI) network was then generated by the Sting database and subjected to Cytoscape software to harvest major and core targets network by topological analysis. Genes from the core targets network were further subjected to Gene Ontology (GO) and KEGG enrichment analysis to figure out potential targeting pathways. Finally, a compounds-targets-pathways network was generated by Cytoscape. A total of 210 active compounds and 768 corresponding potential therapeutic targets were harvested from ingredients of YSNJF. MDS was shown to have 772 potential treating targets with 98 intersected targets corresponding to 98 active compounds in YSNJF. Topological analysis revealed that 15 targets formed the core PPI network. Further, GO and KEGG enrichment analysis revealed that those core targets were mainly enriched on cell cycle- and immune-related pathways. The present study revealed that therapeutic effects of YSNJF on MDS might be achieved through regulating cell cycle- and immune-related pathways.

Resuming Sensitivity of Tamoxifen-Resistant Breast Cancer Cells to Tamoxifen by Tetrandrine.

BACKGROUND: Tamoxifen is one of the medicines for adjuvant endocrine therapy of hormone-dependent breast cancer. However, development of resistance to tamoxifen occurs inevitably during treatment. This study aimed to determine whether sensitivity of tamoxifen-resistant breast cancer cells (TAM-R) could be reinstated by tetrandrine (Tet). METHODS: All experiments were conducted in TAM-R cells derived from the MCF-7 breast cancer cell line by long-term tamoxifen exposure. Cell growth, apoptosis, and autophagy were end-points that evaluated the effect of Tet (0.9 µg/ml, 1.8 µg/ml, and 3.75 µg/ml) alone or in combination with TAM (1 µM). Cell apoptosis was determined by an ELISA assay and autophagy was determined by fluorescent staining using the Enzo autophagy detection kit. Immunoblotting was used to evaluate markers for apoptosis, autophagy, and related signal pathway molecules. RESULTS: Growth of TAM-R cells was significantly inhibited by Tet. Combination of Tet with tamoxifen induced a greater inhibition on cell growth than tamoxifen alone, which was predominantly due to enhancement of pro-apoptotic effect of TAM by Tet. Autophagy was significantly inhibited in TAM-R cells treated with Tet plus TAM as shown by increased autophagosomes and the levels of LC3-II and p62. At 0.9 µg/ml, Tet increased the levels of both apoptosis and autophagy markers. Among them increase in p53 levels was more dramatic. CONCLUSIONS: Tet as a monotherapy inhibits TAM-R cells. Tet potentiates the pro-apoptotic effect of TAM via inhibition of autophagy.