ArticlePloS one2018
Simvastatin and metformin inhibit cell growth in hepatitis C virus infected cells via mTOR increasing PTEN and autophagy.
Article in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
What it found
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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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
29 citing papers in PubMed, 49 citations in OpenAlex.
- Metformin and Time to Sustained Recovery in Adults With COVID-19: The ACTIV-6 Randomized Clinical Trial.JAMA internal medicine · 2025Trial
- Favorable Antiviral Effect of Metformin on SARS-CoV-2 Viral Load in a Randomized, Placebo-Controlled Clinical Trial of COVID-19.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2024Trial
- Randomized Trial of Metformin, Ivermectin, and Fluvoxamine for Covid-19.The New England journal of medicine · 2022Trial
- The synergistic efficacy of lupeol and enzalutamide potentiates anticancer activity, inducing apoptosis and cell cycle arrest in breast cancer cells.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Exploring Autophagy Inducing Molecules: Targeting Diverse Pathways in Alzheimer's Disease Management.Medicinal research reviews · 2026Review
- Advances in the Use of Metformin for Liver Disease.Current medicinal chemistry · 2025Review
- Repurposing of Metabolic Drugs Metformin and Simvastatin as an Emerging Class of Cancer Therapeutics.Pharmaceutical research · 2025Review
- Metformin is a potential therapeutic for COVID-19/LUAD by regulating glucose metabolism.Scientific reports · 2024Article
- A Dual Pharmacological Strategy against COVID-19: The Therapeutic Potential of Metformin and Atorvastatin.Microorganisms · 2024Review
- Mechanistic Insights about Sorafenib-, Valproic Acid- and Metformin-Induced Cell Death in Hepatocellular Carcinoma.International journal of molecular sciences · 2024Review
- The Management of COVID-19-Related Coagulopathy: A Focus on the Challenges of Metabolic and Vascular Diseases.International journal of molecular sciences · 2023Review
- Clinically Evaluated COVID-19 Drugs with Therapeutic Potential for Biological Warfare Agents.Microorganisms · 2023Review
- Article
- Metformin and simvastatin synergistically suppress endothelin 1-induced hypoxia and angiogenesis in multiple cancer types.Cancer science · 2023Article
- Metformin as adjunctive therapy in combination with multidrug treatment for multibacillary leprosy: A protocol for a randomized double-blind, controlled Phase 2 trial in Indonesia (MetLep Trial).Wellcome open research · 2023Article
- mTOR as a Potential Target for the Treatment of Microbial Infections, Inflammatory Bowel Diseases, and Colorectal Cancer.International journal of molecular sciences · 2022Review
- Inhibiting cytomegalovirus replication through targeting the host electron transport chain.Antiviral research · 2021Article
- Outpatient metformin use is associated with reduced severity of COVID-19 disease in adults with overweight or obesity.Journal of medical virology · 2021Article
- A geroscience perspective on immune resilience and infectious diseases: a potential case for metformin.GeroScience · 2021Review
- Sustaining efficient immune functions with regular physical exercise in the COVID-19 era and beyond.European journal of clinical investigation · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hepatitis C virus (HCV) infection has been related to increased risk of development of hepatocellular carcinoma (HCC) while metformin (M) and statins treatment seemed to protect against HCC development. In this work, we aim to identify the mechanisms by which metformin and simvastatin (S) could protect from liver cancer. Huh7.5 cells were infected with HCV particles and treated with M+S. Human primary hepatocytes were treated with M+S. Treatment with both drugs inhibited Huh7.5 cell growth and HCV infection. In non-infected cells S increased translational controlled tumor protein (TCTP) and phosphatase and tensin homolog (PTEN) proteins while M inhibited mammalian target of rapamycin (mTOR) and TCTP. Simvastatin and metformin co-administered down-regulated mTOR and TCTP, while PTEN was increased. In cells infected by HCV, mTOR, TCTP, p62 and light chain 3B II (LC3BII) were increased and PTEN was decreased. S+M treatment increased PTEN, p62 and LC3BII in Huh7.5 cells. In human primary hepatocytes, metformin treatment inhibited mTOR and PTEN, but up-regulated p62, LC3BII and Caspase 3. In conclusion, simvastatin and metformin inhibited cell growth and HCV infection in vitro. In human hepatocytes, metformin increased cell-death markers. These findings suggest that M+S treatment could be useful in therapeutic prevention of HCV-related hepatocellular carcinoma.
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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 Socratic graph.