Introduction: Malignant meningiomas are associated with poor prognosis and limited effective pharmacotherapy. This study aimed to explore potential drugs through drug repurposing based on transcriptomic data and to validate their effectiveness using a malignant meningioma organoid (MMO) model.
Methods: IOMM-Lee cells were used to construct MMOs. The morphology was observed. Proteomics was analyzed using LC-MS/MS. Integrated bioinformatics analysis of transcriptomic data identified candidate drugs using hub genes from protein-protein interaction (PPI) network. Drug susceptibility tests were performed on MMOs and 2D cells. Dose-response curves were generated to compare drug effectiveness between the two models.
Results: MMOs exhibited significant morphological differences from 2D cells. Proteomics analysis showed that there were 36 different enriched gene sets between MMOs and 2D cells, including epithelial-mesenchymal transition (EMT). A PPI network was constructed with 217 nodes and 574 edges, and 10 hub genes were identified. Nine candidate drugs were screened out. Drug susceptibility tests showed that 6 drugs had effectiveness in both MMOs and 2D cells. Paclitaxel and rapamycin demonstrated the greatest efficacy in both models. The effectiveness of some drugs was different between MMOs and 2D cells by comparing IC50 and AUC. Sodium nitroprusside lost its efficacy in MMOs.
Conclusion : Compared to 2D cells, MMOs exhibited a lot of differences including morphology, proteomics, and drug sensitivity. EMT was also observed in MMOs. Paclitaxel and rapamycin showed strong potential in both models, indicating clinical applicability. Future clinical trials should validate the efficacy of these drugs in malignant meningioma patients.
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