Integrative bioinformatics and preliminary experimental validation suggest the therapeutic potential of lycorine in uterine corpus endometrial carcinoma

Uterine corpus endometrial carcinoma (UCEC) is one of the most prevalent gynecological malignancies worldwide and remains a significant threat to women’s health. Lycorine, a natural alkaloid isolated from plants of the Amaryllidaceae family, has attracted considerable attention owing to its diverse pharmacological activities, particularly its anti-tumor properties. However, the potential therapeutic targets and action mechanism of lycorine in UCEC remain unclear. In this study, an integrated strategy combining bioinformatic analysis and preliminary experimental validation was used to elucidate the anti-tumor mechanisms of lycorine in UCEC. Potential targets of lycorine were predicted using public databases and intersected with differentially expressed genes derived from The Cancer Genome Atlas (TCGA) UCEC dataset. Subsequently, a protein–protein interaction (PPI) network was constructed, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were used to investigate the biological functions and pathways associated with these targets. Prognostic analysis and Cox regression were used to establish a risk prediction model. Immune infiltration analysis was performed to evaluate the relationship between key genes and the tumor immune microenvironment. Results revealed 10 potential targets of lycorine associated with UCEC. Functional enrichment analysis indicated that these genes were mainly involved in cholinergic synapse and neuroactive ligand–receptor interaction pathways. Three key genes ( ACHE , MAN2B1 , and PNP ) were further identified to construct a prognostic model, which showed moderate predictive performance in survival analysis. Immune infiltration analysis revealed that these genes were associated with multiple immune cell populations in the tumor microenvironment. Molecular docking revealed that the binding energies of ACHE , MAN2B1 , and PNP with lycorine were ≤ − 7.0 kcal/mol, indicating stable binding. In vitro experiments confirmed that lycorine significantly inhibited the proliferation of Ishikawa endometrial cancer cells. In conclusion, this study provides new insights into the potential therapeutic effects of lycorine in UCEC and identifies ACHE , MAN2B1 , and PNP as promising therapeutic targets for further investigation.