Efficacy and mechanisms of Ci-Gu-Tang against pancreatic cancer: a study using patient-derived models

• The antitumor efficacy of food and medicinal homology species was validated in vitro and in vivo using patient-derived models for the first time. • The efficacy and mechanism of Ci-Gu-Tang in the treatment of pancreatic cancer were elucidated for the first time. • The active constituents and their corresponding targets against pancreatic cancer were explored using network pharmacology, molecular docking, LCMS, and experimental verification. Pancreatic cancer (PC) is a highly lethal disease, and current clinical drugs often have significant side effects. Traditional Chinese medicines, particularly food and medicine homology herbs, present novel opportunities for the development of low-toxicity tumor treatments. It is imperative to further explore the application of these substances in the field of tumor therapy. To investigate the effect of Ci-Gu-Tang (CGT) on pancreatic cancer both in vitro and in vivo and to elucidate its underlying mechanism. In this study, liquid chromatography-mass spectrometry (LC-MS) technology was utilized to validate the constituents of CGT, whereas network pharmacology was employed to further analyze the 37 active ingredients in CGT and their 9 targets associated with PC. Protein-protein interaction (PPI) investigations revealed that the three potential key targets are EGFR, AKT1, and STAT3. Molecular docking was used to elucidate the binding mode and energy between four active ingredients (β-sitosterol, stigmasterol, quercetin, and prangenidin) and the above three targets. Subsequent in vitro and in vivo studies further validated its anti-PC efficacy and confirmed the involvement of the EGFR/AKT1/STAT3 signaling pathway. The utilization of patient-derived organoid (PDO) and patient-derived xenograft (PDX) models enhanced the clinical significance of this investigation. The present research utilized network pharmacology, molecular docking, LCMS, and in vitro and in vivo experiments to examine the effects and mechanism of CGT in the treatment of pancreatic cancer. This study revealed that β-sitosterol, stigmasterol, quercetin, and prangenidin could be practical components by inhibiting tumorigenesis through the EGFR/AKT1/STAT3 axis. PDO and PDX models also demonstrated the effectiveness of CGT. This study represents a pioneering effort in the use of patient-derived models to investigate the potential of food and medicine homology species in cancer treatment.