Exploring the Mechanism of Xihuang Jiedu Capsule in Inhibiting the Growth and Metastasis of Triple-Negative Breast Cancer Based on Network Pharmacology and Experimental Verification
Objective The mechanism of Xihuang Jiedu capsule against triple-negative breast cancer(TNBC)was explored using a network pharmacology approach,with in vivo and in vitro experiments conducted for verification.Methods The active ingredients of Xihuang Jiedu capsule were identified through the Traditional Chinese Medicine Sys-tems Pharmacology Database(TCMSP)and literature review.Corresponding human gene targets of these active ingredients were obtained via the target screening section and the SwissTargetPrediction database.The drug targets were intersected with differentially expressed genes(DEGs)of TNBC obtained from the GEO database(GSE38959)to identify potential tar-gets of Xihuang Jiedu capsule in treating TNBC.These intersecting targets were imported into the STRING online database to construct a PPI network,and core targets were identified based on degree values.GO and KEGG enrichment analyses of these core targets were performed using the DAVID database to explore the possible mechanisms of Xihuang Jiedu capsule in treating TNBC.Western blotting and quantitative real-time PCR(qRT-PCR)were used to detect the expression of key signaling molecules in the signaling pathway in vivo and in vitro.Results Network pharmacology identified core targets of Xihuang Jiedu capsule against TNBC,including HIF1A,VEGFA.The Biological processes mainly involved signal transduc-tion,transcriptional regulation,and proliferation regulation,with participation in pathways such as the cancer signaling path-way,PI3K-Akt signaling pathway,and NF-κB signaling pathway.The experimental results showed that Xihuang Jiedu capsule inhibited the expression of EGFR,AKT(pan),p-AKT(Sei473),NF-κBp65,p-NF-κBp65,PI3Kp85,and PI3Kp110α proteins in 4T1 cells and transplanted tumors.Consistent results were obtained at the genetic level through qRT-PCR experiments.Conclusion Xihuang Jiedu capsule may exert its anti-TNBC effects by inhibiting the PI3K/AKT/NF-κB signaling pathway.
Triple-Negative Breast CancerXihuang Jiedu CapsulesNetwork PharmacologyMechanismCellAnimal
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维普
