Abstract:

Based on network pharmacology, molecular docking, and in vitro experiments, this study explores the molecular mechanism of quercetin against colorectal cancer through the p53 signaling pathway. The drug targets quercetin, and the disease targets colorectal cancer, which was obtained via the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and Gene Cards database, respectively. The common drug and disease targets were mapped using a Venn diagram, and the protein-protein interaction network map was constructed with the help of the String database and Cytoscape_v3.7.2 software. At the same time, GO and KEGG enrichment analysis, molecular docking, core target expression, and survival analysis were also performed. Finally, cell proliferation activity, level of apoptosis, cell cycle arrest, and changes in the expression of core targets and key proteins of the p53 pathway were detected through cellular experiments. Network pharmacology suggests that AKT1 and TP53 are the core targets of quercetin against colorectal cancer, GO and KEGG analysis demonstrate that quercetin is mainly involved in the PI3K/Akt and p53 signaling pathways, molecular docking demonstrates that quercetin exhibits strong binding activity with the core targets AKT1 and TP53, and TP53 is found to be both highly expressed in colorectal cancerand also affect the survival and prognosis of patients with colorectal cancer. The results of cellular experiments show that quercetin can inhibit the proliferation of HCT-116 cells, induce G₀/G₁ cell-cycle arrest in HCT-116 cells, and promote apoptosis. This mechanism may regulate core targets such as TP53 and AKT1, activate the p53 signaling pathway, participate in the proliferation and apoptosis of HCT-116 cells, and thus function to resist colorectal cancer.

Key words: quercetin, colorectal cancer, network pharmacology, molecular docking