Artemisia argyi ethyl acetate fraction suppresses ovarian cancer progression via JUN/MAPK10 signaling: An integrated multi-omics investigation
Artemisia argyi, a traditional Chinese medicinal herb widely applied in gynecology, has recently attracted interest for its pharmacological activities and emerging anti-tumor potential. This study aimed to investigate the inhibitory effects and mechanisms of the ethyl acetate fraction (EA) of A. argyi on ovarian cancer (OvC). Anti-proliferative and anti-migratory effects of EA were evaluated in OvC cell lines (A2780, SKOV3) using CCK-8, colony formation, wound healing, Hoechst 33,258 staining, Annexin V-FITC/PI apoptosis assay, and Western blotting. An A2780 xenograft nude mouse model was employed to assess in vivo efficacy and safety. Integrated transcriptomic, proteomic, and metabolomic analyses were conducted to elucidate mechanisms, with key targets validated by RT-qPCR, Western blot, IHC, and IF. EA-derived components and their plasma availability were profiled using UHPLC-QE Orbitrap-MS. EA markedly inhibited OvC cell proliferation (IC₅₀ = 6.212 and 9.569 μg/ml) and migration, while inducing apoptosis and autophagy. Western blotting showed increased Bax, cleaved Caspase-3, and LC3-II, alongside reduced BCL2 expression. In vivo, EA (15/30 mg/kg) significantly suppressed xenograft tumor growth (39.47 %) without overt toxicity. Multi-omics analysis revealed regulation of Apelin, Oxytocin, cAMP signaling, and arachidonic acid metabolism, identifying JUN and MAPK10 as central targets. Downregulation of JUN, p-JUN, and MAPK10 was validated in tumor tissues by RT-qPCR, WB, IHC, and IF. Sixteen EA-derived components were detected in plasma. The EA fraction of A. argyi exerts potent anti-OvC activity by suppressing proliferation and migration, and by inducing apoptosis via JUN/MAPK10 signaling.