A Clinically Derived TCM Decoction (WD-3) Attenuates Malignant Phenotypes of Gastric Cancer through the PPARγ-AMPK Pathway.

[BACKGROUND & OBJECTIVE] Weitiao No. 3 decoction (WD-3), a clinically used adjuvant therapy for advanced gastrointestinal tumors, lacks clarified mechanisms in gastric cancer (GC).

[METHODS] We profiled chemical constituents by liquid chromatography-mass spectrometry (LC-MS), predicted putative targets and pathways via network pharmacology, evaluated binding by molecular docking, and validated pharmacological effects in MGC-803 cells and mouse xenograft models.

[RESULTS] LC-MS identified 344 constituents; network analyses yielded 188 putative targets and highlighted core nodes (e.g., AKT1, EGFR, PIK3CA, PPARG). Pathway enrichment and docking converged on the PPARγ (PPARG)/AMPK axis. Experimentally, WD-3 suppressed proliferation and migration, induced G1-phase arrest, and increased PPARγ and phospho-AMPK; perturbation of PPARγ modulated AMPK activation and anti-tumor effects. In vivo, high-dose WD-3 reduced xenograft tumor growth in a dose-dependent manner without overt hepato-renal histopathologic toxicity.

[CONCLUSIONS] Using LC-MS, network pharmacology, docking, and in vitro/in vivo assays, we found that WD-3 suppresses GC cell proliferation/migration and xenograft growth, accompanied by increased total PPARγ and AMPK Thr172 phosphorylation, supporting involvement of the PPARγ/AMPK axis.