Abstract

Pancreatic cancer (PC) is a devastating disease with high mortality and a pressing need for safer, less toxic therapies. This study identifies Hui-Xiang decoction (HXD), a formulation from food and medicine homology (FMH) herbs, as an effective and low-toxicity treatment. We identified the presence of 122 active ingredients and 12 PC associated targets in HXD by network pharmacology. HXD and its active component, ammidin, effectively inhibited the proliferation and migration of PC cells. Furthermore, treatment with HXD in clinically relevant patient-derived organoid (PDO) and xenograft (PDX) models significantly inhibited tumor growth, with minimal toxicity. Crucially, we found that HXD combats PC through a dual mechanism: simultaneously inhibiting the oncogenic EGFR/ErbB2/AKT1 pathway and activating the tumor-suppressive Hippo signaling pathway. These results not only elucidate the molecular basis for HXD's efficacy but also provide a strong rationale for its potential application in the management of PC.