Study On The Mechanism Of Guizhi Fuling Pill Combined With Docetaxel In Enhancing Chemotherapy Efficacy Of Triple-negative Breast Cancer Based On PI3K-AKT Signaling Pathwa

Purpose:Using network pharmacology and molecular docking methods to explore the mechanism of action of Guizhi Fuling Pills in the treatment of breast cancer.To investigate the effect of Gui Zhi Fu Ling Wan on breast cancer MDA-MB-231 cell line and the role of chemotherapy in potentiation.To investigate the effect of Gui Zhi Fu Ling Wan on the expression of PI3 K and p-Akt,proteins related to cell proliferation and replication,based on PI3K-AKT pathway.Material andmethod:1.Using network pharmacology and molecular docking methods to explore the mechanism of action of Guizhi Fuling Pills in the treatment of breast cancer.2.Breast cancer MDA-MB-231 cells were cultured in vitro and randomized into blank groups,Guizhi Poria meatballs,docetaxel,and combination groups to interfere with the cells for 24 hours,respectively.(1)In vitro migration of breast cancer cells MDA-MB-231 was observed using cell scratch assays.(2)Changes in the cell cycle of MDA-MB-231 were detected by flow cytometry.(3)ELISA detected expression of PI3 K,p-Akt related proteins in the PI3K-AKT signaling pathway in different groups of MDA-MB-231 cells.(4)Western blot was performed to detect changes in PI3 K and p-Akt expression levels of relevant proteins in the PI3K-AKT signaling pathway in different groups of MDA-MB-231 cells.Results:1.Gui Zhi Fu Ling Wan has multi-component,multi-target and multi-pathway action characteristics in the treatment of breast cancer.Based on network pharmacology and molecular docking,verified that PI3K-AKT pathway,AGE-RAGE signaling pathway,chemical carcinogenesis-receptor activation and IL-17 signaling pathway are related to its anti-breast cancer mechanism.2.Cell scratch experiments and calculation of scratch healing rates showed that Cassiophane Pill inhibited the migration of MDA-MB-231 cells,and Cassiophane Pill in combination with docetaxel further inhibited the migration.3.Flow cytometry showed that Cassia zhipora could block MDA-MB-231 cells in S-phase.The effect of Guizhifuling pill combined with the chemotherapy drug docetaxel on S-phase was more obvious than docetaxel alone.4.Enzyme-linked immunoassays and protein imprinting showed that Guizhifulin caused downregulation of PI3 K and p-Akt associated proteins in the PI3K-Akt signaling pathway,and the combination of Guizhifulin and docetaxel resulted in further downregulation of PI3 K and p-Akt associated proteins involved in cell proliferation and replication in the PI3K-Akt signaling pathway compared to docetaxel alone..Conclusion:1.Using network pharmacology and molecular docking methods to explore the mechanism of action of Guizhi Fuling Pills in the treatment of breast cancer.2.Guizhifuling Pill inhibits MDA-MB-231 migration and inhibits breast cancer cell cycle in S-phase,thereby inhibiting cell proliferation replication and thereby synergizing docetaxel chemotherapy in breast cancer.3.The inhibition of replication and proliferation of MDA-MB-231 in breast cancer cells and the synergistic effects of docetaxel chemotherapy may be associated with downregulation of expression of PI3 K and p-Akt related proteins in the PI3K-Akt signaling pathway.