Molecular Mechanisms of Buzhong Yiqi Decoction in the Treatment of Gastric Cancer: A Network Pharmacology, Molecular Docking, and In Vitro Experimental Analysis

Abstract

ABSTRACTGastric cancer (GC) is the most common type of cancer of the digestive system with high morbidity and mortality. Chemotherapy and targeted therapy are used to treat patients with advanced GC. However, side effects and drug resistance to the two modalities remain the main challenges. The Buzhong Yiqi decoction (BZYQD), a classical traditional Chinese medicine formula, has been reported for the treatment of various types of cancers. However, the underlying pharmacological mechanism has not been fully elucidated. Therefore, this study integrated network pharmacology, molecular docking, cancer public databases, and cell experiments to explore the potential bioactive compounds and BZYQD's mechanism of action against GC. A total of 245 targets of BZYQD, 5291 GC‐related targets, and 186 were identified as their common targets through the database. Network analysis confirmed AKT1, TP53, TNF, and EGFR to be the core targets, while the main compounds observed were quercetin, kaempferol, and β‐Sitosterol. The core signaling pathways included PI3K‐AKT, MAPK, TNF, and IL‐17. Molecular docking revealed good binding activity for the main compounds and core targets. Based on the database's validation of core targets, a large number of core genes were verified to be consistent with this study. Quercetin, kaempferol, and β‐Sitosterol were found to significantly reduce the growth of GC cells in the MTT experiment. The current study revealed that BZYQD may inhibit GC progression by interfering with core targets such as AKT1, TP53, TNF, EGFR, and MAPK3, and by regulating the activity of PI3K‐AKT, MAPK, TNF, and IL‐17 signaling pathways.