Unraveling the therapeutic potential of triptolide in glioma: Orchestrating apoptosis and immune landscape remodeling.

BACKGROUND

Glioma is a highly aggressive brain tumor marked by rapid proliferation, therapy resistance, and an immunosuppressive microenvironment. Triptolide, a bioactive compound from Tripterygium wilfordii, has demonstrated anticancer potential, yet its mechanisms in glioma remain unclear.

METHODS

We integrated transcriptomic analysis, immune infiltration profiling, and experimental validation. Differentially expressed genes from GSE147352 were intersected with triptolide targets, and hub genes were identified via protein-protein interaction network analysis. Functional enrichment (GO and KEGG) and immune cell infiltration analyses were performed. Single-cell RNA sequencing validated immune-related changes, and immunohistochemistry confirmed protein-level differences. Key targets were further validated by qPCR in glioma cells.

RESULTS

Forty-seven intersecting genes were identified, enriched in apoptosis, inflammation, and immune regulation pathways. Triptolide promoted glioma cell apoptosis by modulating BCL2L11, CASP3, MCL1, and TNF, while reprogramming the immune microenvironment by regulating IL6, IL-1β, IL10, and TGF-β1, thereby suppressing M2 macrophage polarization. Single-cell analysis confirmed these findings, and qPCR validated transcriptional changes.

CONCLUSION

Triptolide exerts dual anti-glioma effects by inducing apoptosis and reshaping the tumor immune microenvironment. By shifting macrophages toward a pro-inflammatory M1 phenotype and activating apoptotic pathways, triptolide emerges as a promising candidate for glioma immunotherapy.