In this study,UPLC-Q-TOF-MS/MS technology and network pharmacology strategy were used to explore the pharmacodynamic material basis and mechanism of anti-breast cancer of petroleum ether fraction of Alocasia cucullata (EAC).The anti-breast cancer effect and mechanism of EAC in vivo were verified by 4T1 breast cancer tumor-bearing mouse model.Based on UPLC-Q-TOF-MS/MS data,41 chemical components of EAC were identified,including 11 aromatic compounds,8 terpene compounds,5 alkaloid compounds,4 fatty acid compounds,2 coumarin compounds,and 11 other compounds.Network pharmacology identified 556 potential target proteins for the identified compounds.PPI analysis identified 10 core targets,including MAPK1 and Bcl-2.Enrichment analysis suggested that these core targets might exert anticancer effects through pathways like MAPK and PI3K-Akt,related to cell apoptosis.Molecular docking confirmed the strong binding ability of active components like digitoxigenin with apoptosis-related proteins such as pERK,Bcl-2,and Bax.The results of the anticancer activity study showed that compared to the model group,the tumor growth trend was slower in the low,medium,and high-dose EAC groups.Tumor mass decreased,and the tumor inhibition rate increased gradually.The spleen index showed significant differences in the medium and high-dose EAC groups,while the low-dose EAC group did not show significant effects (P <0.05).HE staining revealed loosely arranged cells with unclear outlines in the tumor tissues of the treated groups.ELISA analysis of mouse serum revealed decreased levels of IL-1β and TNF-α in the high and medium-dose EAC groups,as well as in the positive control group treated with 5-fluorouracil.Animal validation experiments demonstrated that EAC,at different concentrations,downregulated the expression of p-ERK protein in the MAPK signaling pathway (P <0.01),with no significant differences observed in the levels of ERK,JNK,p-38,p-JNK,and p-p38 proteins.EAC significantly increased the levels of Bax/Bcl-2 proteins and gene expression in mouse breast cancer tissues.In conclusion,EAC can down-regulate p-ERK protein levels,promote cancer cell apoptosis,and inhibit the growth of 4T1 breast cancer tumors in mice.