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Oral squamous cell carcinoma (OSCC) has a poor prognosis and limited effective therapies. Anemarrhena asphodeloides exhibits anticancer activity, but its efficacy in OSCC treatment remains underexplored. Network and protein-protein interaction analysis identified 275 overlapping targets and 12 hub genes, with HSP90AA1, HSP90AB1, and CASP3 upregulated in OSCC, linked to poorer survival. QSAR modeling, molecular docking, and molecular dynamics simulations demonstrated stable binding of key bioactive compounds with HSP90 and AKT1, highlighting hippeastrine as a promising candidate. ADMET analysis indicated their favorable pharmacokinetic profiles. To validate the therapeutic potential of hippeastrine, in vitro experiments were conducted using the CAL27 and SCC-9 cell lines. CCK-8 assay demonstrated that hippeastrine exerted significant and dose-dependent cytotoxicity against OSCC cells. Furthermore, hippeastrine treatment significantly suppressed colony formation and attenuated cell migration and invasion capabilities. Gene set enrichment analysis of TCGA-HNSC data revealed a positive correlation between HSP90AA1/AB1 expression and PI3K/Akt/mTOR signaling. Western blot analysis confirmed inhibition of the HSP90-PI3K-Akt-mTOR axis by hippeastrine. Moreover, functional rescue experiments with the PI3K activator 740 Y-P successfully reversed the hippeastrine-induced suppression of cell viability and PI3K/Akt phosphorylation. These findings indicate that hippeastrine exerts anti-OSCC effects by targeting the HSP90/PI3K/Akt/mTOR pathway, highlighting it as a novel therapeutic agent against OSCC.
Lu et al. (Sat,) studied this question.