Affiliation:
1. Tibet University Medical College, Lhasa, Tibet, 850000, China
2. Lhasa People's Hospital, Lhasa, Tibet, 850000,
China
3. School of Medicine, Chongqing University, Chongqing, 404100, China
Abstract
Background:
Network pharmacology is a novel approach that uses bioinformatics to
predict multitarget drugs and ingredient-target interactions in various diseases. A thorough
search of previously published studies revealed that Hedyotis diffusa Willd (HDW) and Astragalus membranaceus (AM) possess anticancer activity. Colon cancer (CC) is one of the most
common malignant tumors of the digestive tract and occurs in the colon. Herein, we explored
the effect of two drugs in the treatment of CC.
Objective:
The present study aimed to predict and verify the effect of these two drugs in the
treatment of CC.
Methods:
To explore the molecular mechanisms of the “HDW-AM” drug in the treatment of
CC, we analyzed its principal efficiency in terms of ingredients, target spots, and pathways via
network pharmacology, molecular docking, and experimental verification. The ingredients and
their gene target sites were searched and screened through the TCMSP platform according to
specific filtering conditions. Subsequently, components corresponding to the gene targets were
chosen to construct the drug component-target network. The GEO (Gene Expression Omnibus)
dataset was used to collect and screen for gene chips under CC and normal conditions, obtain
differential genes, and construct a volcano map. The intersection genes between drug and disease targets were screened, the “.tsv” file was downloaded from the STRING platform and imported into Cytoscape 3.8.0 for visualization, a protein-protein interaction (PPI) network was
constructed, the core targets were identified, and the common components with core targets
were docked through Autodock Tools-1.5.6. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were carried out through the Metascape platform
to determine the major pathways. The CCK-8 (Cell Counting Kit-8) assay verified the effect of
AKT1 on cell proliferation after treatment with quercetin.
Results:
After the screening, 3658 DEGs (1841 downregulated and 1817 upregulated) were obtained from the GSE75970 gene chip; 21 active components and 220 targets were identified
from the drugs. Subsequently, ten core genes (including AKT1, P53, and CASP3) and six major
components were screened. GO functional analysis and KEGG analysis revealed that “HDWAM” regulates cell migration and motility through the combination of a transcription regulator
complex, membrane rafts, vesicle lumen, and protein kinases via the MAPK, PI3K-Akt, and IL17 signaling pathways. The molecular docking results suggested that quercetin binds to AKT1,
TP53, TNF, and CASP3. HDW-AM may exert a therapeutic effect on CC by modulating AKT1,
TP53, TNF, and CASP3 and through signaling pathways. A CCK-8 cytotoxicity assay verified
that quercetin affects cell viability through AKT1.
Conclusions:
The current study provides a theoretical basis for an in-depth investigation into
the molecular mechanism of the “HDW-AM” drug in CC treatment via network pharmacology,
molecular docking, and experimental verification.
Publisher
Bentham Science Publishers Ltd.