Network Pharmacology, Molecular Docking, and Experimental Validation to Investigate the Mechanism of Qifu Longkui Decoction in the Treatment of Colorectal Cancer
Authors: Xiong Yaling , Liu Yihao , Chen Xia , Tang Shuiwen , Jian Zhiyuan 
Published: December 2024

Objective

This study aimed to validate the potential targets of QLD for treating CRC and explore its possible therapeutic mechanism through network pharmacology, molecular docking, and experimental validation.

Methods

The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), the Traditional Chinese Medicine Information Database (TCMID), a literature search, and the SwissTargetPrediction database were used to identify the active components and potential targets of QLD. The Online Mendelian Inheritance in Man (OMIM), GeneCards, and DrugBank databases were utilized for CRC target identification. Common targets in CRC and QLD were subsequently screened via a Venn diagram. Next, the Search Tool for the Retrieval of Interacting Genes/Genomes (STRING) database was used to perform protein-protein interaction (PPI) network analysis of the common targets. Gene Ontology (GO) functions and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were employed to identify signaling pathways. After that, “drug-component-target” networks were built via Cytoscape 3.9.1 [2024.3.2]. AutoDock Tools 1.5.7 [2024.4.6] and PyMoL 2.4.0 [2024.4.13] were utilized for molecular docking to analyze the relationships between the active ingredients and core targets. Later, in vitro experiments were performed to validate the anticancer effects of QLD on CRC.

Results

Network pharmacology analysis revealed 200 active components and 194 potential targets of QLD from the TCMSP database. Disease target databases predicted 1590 targets associated with CRC. The potential anti-colorectal cancer mechanism of QLD may involve lipid and atherosclerosis, chemical carcinogenesis-receptor activation, HIF-1 signaling pathway, TNF signaling pathway, cellular senescence, EGFR tyrosine kinase inhibitor resistance, platinum drug resistance, and the FoxO signaling pathway. Furthermore, QLD has a therapeutic effect through its effects on the 6 core targets TP53, AKT1, TNF, EGFR, IL6 and CASP3. Kaempferol is an active ingredient of QLD and is a flavonoid compound that is known for its antitumor, antioxidant and anti-inflammatory effects. It is unclear how kaempferol affects the onset of CRC. 1 In this study, when the concentration of kaempferol was 2 mg/mL, the proliferative capacity of colorectal cancer cells was inhibited, and kaempferol regulated the AKT/CyclinD1 pathway to inhibit the proliferation of Caco-2 cells.

Conclusions

Network pharmacology approaches in cancer therapy are highly beneficial. 2 This approach serves as an effective supplementary method for identifying multiple targets of QLD and the underlying mechanisms involved in the fight against CRC. This research reveals the potential role of QLD in the treatment of CRC from a network pharmacology perspective for the first time, enhances the knowledge regarding QLD and offers new insight into QLD research for CRC treatment.