Traditional Chinese Medicinal Leech Induces Apoptosis and Autophagy in Glioblastoma by SGK1/Caspase-3 and PI3K/AKT/mTOR Pathway

BACKGROUND: Glioblastoma (GBM) represents the most lethal form of high-grade glioma, with current therapeutic options proving largely ineffective. Consequently, there is an urgent need for novel treatment strategies. Recent studies have indicated that the medicinal leech exhibits notable anticancer properties. However, the precise mechanisms underlying these effects remain to be elucidated. METHODS: To investigate the impact of leech drug-containing serum (LDS) on the proliferation, migration, and invasion of GBM cells, a series of assays including CCK-8, ethynyl deoxyuridine (EdU), colony formation, scratch, and transwell assays were employed. Additionally, the apoptosis and autophagy of GBM cells were analyzed using flow cytometry, monodansylcadaverine staining and the immunofluorescence assay. Transcriptomic sequencing of the cells was conducted to identify differentially expressed genes. In vivo, anticancer activity was assessed by developing tumor xenograft models. Western blot analysis was utilized to identify proteins associated with apoptosis and autophagy. RESULTS: Leech drug-containing serum (LDS) significantly inhibited proliferation, migration, and invasion. Furthermore, it induced autophagy and apoptosis in GBM. Differential gene enrichment analysis and pathway validation indicated that LDS exerts anti-GBM effects by modulating the PI3K/AKT pathway. Leech extracts effectively inhibit the growth of GBM in a subcutaneous xenograft tumor model. CONCLUSION: The leech-derived compounds may induce apoptosis and autophagy in GBM by modulating the PI3K/AKT/mTOR signaling pathway, without eliciting significant adverse effects, thereby presenting itself as a promising therapeutic agent.

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Treating glioblastoma cells with leech drug-containing serum reduced their proliferation, migration and invasion while triggering apoptosis and autophagy; leech extract also inhibited tumor growth in a subcutaneous xenograft model, with anti-GBM effects potentially involving the PI3K/AKT/mTOR and SGK1/Caspase-3 pathways, without significant adverse effects.

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