Objective This study aims to investigate the molecular mechanisms underlying the antimetastatic effects of Akebia trifoliata root (ACPS), a traditional Chinese herbal medicine, on gastrointestinal stromal tumors (GIST). Methods An integrated approach combining network pharmacology, GEO transcriptomic datasets, and molecular docking was employed to identify bioactive compounds in ACPS and their potential gene targets. Functional enrichment analyses were conducted, followed by in vitro experiments using GIST cell lines and profiling of the tumor immune microenvironment. Results Six bioactive compounds from ACPS were identified, targeting 34 key genes involved in cell‐cycle regulation and immune responses. Among these, three lead compounds demonstrated strong binding affinities to four critical targets. In vitro assays confirmed that ACPS inhibited GIST cell proliferation, invasion, and cell‐cycle progression. Additionally, seven immune‐related targets were identified, suggesting ACPS may modulate the tumor immune microenvironment. Conclusion ACPS exhibits multitarget therapeutic potential against metastatic GIST by disrupting cell‐cycle signaling and modulating immune responses within the tumor microenvironment (TME). These findings support further investigation into ACPS as a complementary or alternative therapeutic strategy for GIST.
Yu et al. (Thu,) studied this question.