Exploration of Dan-Shen-Yin against pancreatic cancer based on network pharmacology combined with molecular docking and experimental validation

• Published in: Current research in biotechnology 2024, Vol.7, p.100228, Article 100228
• Main Authors: Gu, Ao, Li, Jiatong, Wu, Jian-An, Li, Meng-Yao, Liu, Yingbin
• Format: Article
• Language: English
• Subjects: Dan-Shen-Yin (DSY); EGFR/SRC/STAT3 signaling; Network pharmacology; pancreatic cancer (PC); patient-derived xenograft (PDX)
• ISSN: 2590-2628; 2590-2628
• DOI: 10.1016/j.crbiot.2024.100228

Traditional Chinese medicine (TCM) in cancer treatment has brought a new era of low-toxicity therapy. However, further research is needed to explore the relationship between active components and related targets. Network pharmacology is a powerful tool for exploring the potential action mechanisms of TCMs and new active ingredients, but in vivo efficacy validation, especially clinically meaningful evidence, remains infrequent. The cell-derived xenograft (CDX) model is commonly used to validate network pharmacology but cannot present intratumoral heterogeneity. Patient-derived xenograft (PDX) models are a promising alternative due to their ability to maintain the original tumor’s fundamental histological and genetic characteristics. It is imperative to utilize PDX models to validate network pharmacology’s clinical potential. Herein, treating pancreatic cancer (PC) with Dan-Shen-Yin (DSY) as an example, we validated network pharmacology analysis employing the PDX model. 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 DSY effectively inhibited tumor growth and improved prognosis. In conclusion, the PDX model verifies network pharmacology’s efficacy and clinical value. Both in vivo and in vitro assays confirmed that the DSY formula effectively treated PC by inhibiting EGFR / SRC /STAT3 signaling and anti-apoptotic pathways. [Display omitted] •The anti-pancreatic cancer effect of Dan-Shen-Yin (DSY) has not been previously reported. We have conducted in vitro and in vivo experiments to validate the effect.•The anti-pancreatic cancer mechanism of DSY was elucidated through the integration of network pharmacology, molecular docking, and experimental validation.•Using the patient-derived xenograft (PDX) model to study DSY’s anti-pancreatic cancer effects is clinically important. This represents the pioneering application of the PDX model in traditional Chinese medicine for cancer treatment. Traditional Chinese Medicine (TCM) introduces a potentially effective strategy in the realm of cancer therapy, whereas network pharmacology provides a reliable mecha