Related Experiment Video
Updated: Jan 27, 2026
Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
Published on: October 27, 2020
Statins affect human glioblastoma and other cancers through TGF-β inhibition
Aizhen Xiao1, Breanna Brenneman1, Desiree Floyd1
1Departments of Neurology, University of Virginia, Charlottesville, VA 22908, USA.
Abstract:
The cholesterol-lowering statins have known anti-cancer effects, but the mechanisms and how to utilize statins in oncology have been unclear. We noted in the CellMiner database that statin activity against cancer lines correlated with higher expression of TGF-β target genes such as SERPINE1 and ZYX. This prompted us to assess whether statins affected TGF-β activity in glioblastoma (GBM), a cancer strongly influenced by TGF-β and in dire need of new therapeutic approaches. We noted that statins reduced TGF-β activity, cell viability and invasiveness, Rho/ROCK activity, phosphorylation and activity of the TGF-β mediator Smad3, and expression of TGF-β targets ZYX and SERPINE1 in GBM and GBM-initiating cell (GIC) lines. Statins were most potent against GBM, GIC, and other cancer cells with high TGF-β activity, and exogenous TGF-β further sensitized mesenchymal GICs to statins. Statin toxicity was rescued by addition of exogenous mevalonolactone or geranylgeranyl pyrophosphate, indicating that the observed effects reflected inhibition of HMG CoA-reductase by the statins. Simvastatin significantly inhibited the growth of subcutaneous GIC grafts and prolonged survival in GIC intracranially grafted mice. These results indicate where the statins might best be applied as adjunct therapies in oncology, against GBM and other cancers with high TGF-β activity, and have implications for other statin roles outside of oncology.
Insights
Statins show anti-cancer effects by reducing transforming growth factor-beta (TGF-β) activity, particularly in glioblastoma. These findings suggest statins as potential adjunct therapies for cancers with high TGF-β signaling.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Cholesterol-lowering statins possess anti-cancer properties, but their mechanisms and therapeutic applications in oncology remain unclear.
- Transforming growth factor-beta (TGF-β) signaling plays a significant role in glioblastoma (GBM) development and progression.
- Identifying novel therapeutic strategies for GBM is critical due to its aggressive nature and limited treatment options.
Purpose of the Study:
- To investigate the anti-cancer mechanisms of statins, focusing on their impact on TGF-β activity in glioblastoma.
- To determine the correlation between statin efficacy and TGF-β target gene expression in cancer cell lines.
- To evaluate the potential of statins as adjunct therapies for GBM and other TGF-β-driven cancers.
Main Methods:
- Analysis of the CellMiner database to identify correlations between statin activity and TGF-β target gene expression (e.g., SERPINE1, ZYX).
- In vitro studies using glioblastoma (GBM) and glioblastoma-initiating cell (GIC) lines to assess statin effects on TGF-β activity, cell viability, invasiveness, Rho/ROCK signaling, and Smad3 phosphorylation.
- In vivo studies involving subcutaneous and intracranial GIC grafts in mice to evaluate simvastatin's efficacy in inhibiting tumor growth and prolonging survival.
Main Results:
- Statins reduced TGF-β activity, cell viability, invasiveness, Rho/ROCK activity, Smad3 phosphorylation, and expression of TGF-β targets (ZYX, SERPINE1) in GBM and GIC lines.
- Statin potency was highest in cancer cells exhibiting high TGF-β activity; exogenous TGF-β sensitized mesenchymal GICs to statins.
- Statin-induced toxicity was reversed by mevalonolactone or geranylgeranyl pyrophosphate, confirming HMG CoA-reductase inhibition.
- Simvastatin significantly inhibited GIC graft growth and improved survival in mouse models of GBM.
Conclusions:
- Statins effectively inhibit TGF-β signaling and exhibit anti-cancer effects in glioblastoma models.
- Statins are most effective against cancers with high TGF-β activity, positioning them as potential adjunct therapies for GBM and similar malignancies.
- These findings have implications for expanding the therapeutic roles of statins beyond cholesterol management, particularly in oncology.
Related Concept Videos
01:16TGF - β Signaling Pathway
01:24Role of Affect in Interpersonal Attraction
00:46Feedback Inhibition
01:29The Influence of Affect on Cognition
01:29The Influence of Cognition on Affect
01:20Lipid-Lowering Drugs: Statins and Miscellaneous Agents