Aim of the study
To investigate the therapeutic mechanism of KLP in the treatment of gliomas. Materials and
Conclusion
Therapeutic effect of KLP was regulation of multiple pathways in the treatment of gliomas. In specific, it interacts through the PI3K-Akt signaling pathway. This work may contribute proteomic insights for further research on the medical treatment of glioma using KLP.
Methods
An in situ xenograft model of red fluorescent protein-labeled human glioma cell line (U87-RFP) in BALB/c-nu mouse was established, and the therapeutic effect of KLP on gliomas was assessed by tumor weights and fluorescence areas. A quantitative proteomics approach using tandem mass tags combined with liquid chromatography-tandem mass spectrometry was performed to explore differentially expressed proteins (DEPs) in glioma tissues, and bioinformatics analyses including Gene Ontology analysis, pathway analysis, and network analysis were performed to analyze the proteins involved in the network therapeutic mechanisms responsible for key metabolic pathways. Cytological experiments corroborated the above analysis
Results
Network pharmacology approach screened 246 bioactive compounds contained in KLP, targeting 724 proteins and 173 potential targets of KLP for glioma treatment. The important targets obtained after visualizing the PPI network were AKT1, INS, GAPDH, SRC, TP53, etc. The KEGG enrichment results showed that 9 proteins were related to cancer, including Pathways in cancer, PI3K/AKT signaling pathway, etc. KLP had antitumor activity in gliomas, which reduced tumor weights and fluorescence areas. A number of DEPs possibly associated with gliomas were identified through quantitative proteomic techniques. Among these DEPs, 50 (25 upregulated and 25 downregulated) were identified that might be associated with KLP action. Bioinformatics showed that these 50 DEPs were mainly focused on focal adhesion, extracellular matrix (ECM)-receptor interactions, and the PI3K-Akt signaling pathway. Cytological experiments revealed that KLP significantly inhibited the proliferation and promoted apoptosis of U87-MG human glioma cells, and its mechanism was through the inhibition of PI3K/AKT signaling pathway.