ArticleDigestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver2011
Simvastatin stimulates apoptosis in cholangiocarcinoma by inhibition of Rac1 activity.
Article in Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.
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Who cites it
31 citing papers in PubMed, 1 synthesis or guideline pooled it, 53 citations in OpenAlex.
- Statins associate with lower risk of biliary tract cancers: A systematic review and meta-analysis.Cancer medicine · 2023Pooled it
- Trial
- RAC1 signaling in polyploid giant cancer cells: Implications for tumorigenesis and therapy resistance.Cancer letters · 2026Review
- Repurposing statins for choriocarcinoma: targeting the mevalonate pathway to disrupt mechanosignaling and overcome therapeutic resistance.Clinical & experimental metastasis · 2026Review
- Article
- Correlation between dyslipidaemia and gastric cancer: pathogenesis to prevention and treatment strategies.Lipids in health and disease · 2025Review
- Statins as Secondary Preventive Agent to Limit Breast Cancer Metastatic Outgrowth.International journal of molecular sciences · 2025Review
- Review
- Repositioning of HMG-CoA Reductase Inhibitors as Adjuvants in the Modulation of Efflux Pump-Mediated Bacterial and Tumor Resistance.Antibiotics (Basel, Switzerland) · 2023Review
- Simvastatin Induces Apoptosis And Suppresses Hepatocellular Carcinoma Induced In Rats.Applied biochemistry and biotechnology · 2023Article
- RAC1 Activation as a Potential Therapeutic Option in Metastatic Cutaneous Melanoma.Biomolecules · 2021Review
- Statins: a repurposed drug to fight cancer.Journal of experimental & clinical cancer research : CR · 2021Review
- Statin as a Potential Chemotherapeutic Agent: Current Updates as a Monotherapy, Combination Therapy, and Treatment for Anti-Cancer Drug Resistance.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Pleiotropic effects of statins: A focus on cancer.Biochimica et biophysica acta. Molecular basis of disease · 2020Review
- Effect of Statins on the Risk of Extrahepatic Cholangiocarcinoma.Hepatology (Baltimore, Md.) · 2020Article
- Inhibition of growth and migration of cholangiocarcinoma cells by pamidronate.Experimental and therapeutic medicine · 2019Article
- Downregulation of ABCA1 and ABCG1 transporters by simvastatin in cholangiocarcinoma cells.Oncology letters · 2019Article
- Review
- Pro-metastatic signaling of theOncology letters · 2018Article
- Cholesterol and Its Metabolites in Tumor Growth: Therapeutic Potential of Statins in Cancer Treatment.Frontiers in endocrinology · 2018Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundSimvastatin is a cholesterol-lowering drug that is widely used to prevent and treat atherosclerotic cardiovascular disease. Simvastatin exhibits numerous pleiotropic effects including anti-cancer activity. However, the effect of simvastatin on cholangiocarcinoma has not been evaluated.
aimThe aim of our study was to determine the effect of simvastatin on cholangiocarcinoma proliferation.
methodsThe effect of simvastatin was evaluated in five human cholangiocarcinoma cell lines (Mz-ChA-1, HuH-28, TFK-1, SG231, and HuCCT1) and normal cholangiocyte cell line (HiBEpiC).
resultsWe found that simvastatin stimulates a reduction in cell viability and apoptosis of cholangiocarcinoma cell lines, whilst in normal human cholangiocytes, HiBEpiC, simvastatin inhibits proliferation with no effect on apoptosis. Simvastatin-induced reduction of cell viability was partially blocked by pre-treatment with metabolites of the mevalonate pathway. In Mz-ChA-1 cells, pre-treatment with cholesterol alone stimulated an increase in the number of viable cells and fully restored cell viability following simvastatin treatment. Treatment with simvastatin triggered the loss of lipid raft localised Rac1 and reduction of Rac1 activity in Mz-ChA-1 cells. This effect was prevented by pre-treatment with cholesterol.
conclusionCollectively, our results demonstrate that simvastatin induces cholangiocarcinoma cancer cell death by disrupting Rac1/lipid raft colocalisation and depression of Rac1 activity.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.