Mechanism of Quercetin and Luteolin on Colon Cancer Metastasis: Network Pharmacological Study and Experimental Validation

Quercetin (QCT) and luteolin (LTL) are anticancer herbal compounds. However, their combined effects on colon cancer metastasis remain unknown. This study explored the effects and mechanisms of QCT and LTL against colon cancer metastasis using network pharmacology and experimental validation. We systematically screened 74 QCT and LTL targets from the TCMSP, HERB, SwissTargetPrediction, TCGA, and GeneCards databases, which intersected with colon cancer metastasis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed to investigate the biological processes and pathways of QCT and LTL. These analyses revealed that QCT and LTL modulate 119 pathways, and that of these, the PTK2/PI3K/Akt pathway was associated with resistance to colorectal cancer metastasis. Experimental validation demonstrated that the combination of QCT and LTL inhibited the anchorage-independent growth, adhesion, migration, and invasion of CT26 cells. The combined treatment also induced caspase-dependent anoikis in CT26 cells. In addition, QCT and LTL synergistically inhibited the lung metastasis of CT26 colon cancer in vivo. Furthermore, Western blot analysis and immunohistochemical detection identified that QCT and LTL inhibited the phosphorylation of PTK2/PI3K/Akt. These findings provide a basis for the application of QCT and LTL for the treatment of colon cancer metastasis.