ArticleJournal of neuro-oncology2025
Synergistic activity of simvastatin and irinotecan chemotherapy against glioblastoma converges on TGF-β signaling.
Article in Journal of neuro-oncology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
1 citing paper in PubMed.
- ZBTB20 promotes ferroptosis through inhibiting TMEM109 expression in glioblastoma cells.International journal of oncology · 2025Article
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8 authors.
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Abstract
purposeThis study investigates the synergistic therapeutic potential of a novel combination of the repurposed drug simvastatin with irinotecan chemotherapy towards glioblastoma (GBM) and the underlying molecular mechanisms.
methodsIn vitro efficacy of simvastatin and irinotecan alone and in combination against diverse GBM lines (U251MG, G34, SB28) was assessed using mechanistically distinct cell viability assays. RNA-Sequencing was performed to uncover the top pathways and genes affected by these drugs, followed by validation of promising pathways (TGF-β signaling and cell death) using targeted phosphoproteomics and in vitro genetic manipulation and functional assays.
resultsWe observed robust in vitro synergy at nanomolar concentrations between simvastatin and irinotecan across diverse GBM lines. Notably, irinotecan alone and in combination with simvastatin reduced mRNA expression of TGF-β family members. Targeted phosphoproteomics and functional experiments further showed significant inhibition of TGF-β signaling with both treatment types. Additionally, a role for apoptosis and enrichment of caspase-independent cell death pathways (autophagy, ferroptosis) as well as immunological (interferons, complement, inflammatory responses, TNF-α) and oncogenic (K-RAS/ERK) signaling pathways were observed with the combination treatment.
conclusionsBesides the first detailed demonstration of a robust synergy between simvastatin and irinotecan against GBM lines, this study shows for the first time that both irinotecan and the combination treatment converge on inhibition of TGF-β signaling. This is notable given the lack of TGF-β inhibitors in the clinic. Collectively, this study provides preclinical data suggesting this novel drug combination be tested in patients with GBM and TGF-β driven cancers.
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