Exploration of Dan-Shen-Yin against pancreatic cancer based on network pharmacology combined with molecular docking and experimental validation
Ao Gu, Jiatong Li, Jian-An Wu, Mengyao Li, Yingbin Liu
Abstract
Traditional Chinese Medicine (TCM) introduces a potentially effective strategy in the realm of cancer therapy, whereas network pharmacology provides a reliable mechanism for clarifying the complex interplay between active constituents and their corresponding targets. Although Dan-Shen-Yin (DSY) has demonstrated remarkable efficacy in the treatment of various diseases, its potential anti-pancreatic cancer effects and underlying mechanisms remain unexplored. The present study aims to validate the anti-pancreatic cancer efficacy of DSY both in vivo and in vitro, while also elucidating its mechanism through a combination of network pharmacology, molecular docking, and related experiments. The in vivo effectiveness of DSY was validated using the patient-derived xenograft (PDX) model, which was chosen due to its remarkable capacity to maintain the essential histological and genetic attributes of the primary tumor. Network pharmacology predicted the anti-pancreatic cancer efficacy of DSY, which was confirmed by in vitro experiments showing inhibitory effects on proliferation, pro-apoptosis, migration, and colony formation of PC cells. Molecular docking studies further confirmed that the active components of DSY exhibited good nucleophilicity for the selected target proteins through their ability to interact via hydrogen bonding and Van der Waals forces. The PDX model showed that DSY effectively inhibited tumor growth and improved prognosis. Experiments conducted both in vivo and in vitro have demonstrated that DSY is an effective treatment for PC. Moreover, mechanistic investigations have provided evidence of the ability to impede the EGFR/SRC/STAT3 signaling pathway.