ArticleJournal of experimental & clinical cancer research : CR2020
Simvastatin re-sensitizes hepatocellular carcinoma cells to sorafenib by inhibiting HIF-1α/PPAR-γ/PKM2-mediated glycolysis.
Article in Journal of experimental & clinical cancer research : CR, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 163 papers, 5 of them syntheses that pooled it.
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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.
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Who cites it
163 citing papers in PubMed, 5 syntheses or guidelines pooled it, 227 citations in OpenAlex.
- Prognostic evaluation of glycolysis markers in hepatocellular carcinoma: insights from meta-analysis and multi-omics approaches.BMC medical genomics · 2025Pooled it
- Statin Use and Hepatocellular Carcinoma Risk: A Comprehensive Meta-Analysis and Systematic Review.Recent patents on anti-cancer drug discovery · 2025Pooled it
- The Influence of Statin Use on Chemotherapeutic Efficacy in Studies of Mouse Models: A Systematic Review.Anticancer research · 2023Pooled it
- Statins Are Associated with Improved Survival of Patients with Gastric Cancer: A Systematic Review and Meta-Analysis.International journal of clinical practice · 2022Pooled it
- First-Line Systemic Treatment Strategies for Unresectable Hepatocellular Carcinoma: A Systematic Review and Network Meta-Analysis of Randomized Clinical Trials.Frontiers in oncology · 2021Pooled it
- Pachymic acid exhibits synergistic antitumor efficacy with lenvatinib in hepatocellular carcinoma by targeting PPARγ to inhibit glycolysis.Medical oncology (Northwood, London, England) · 2026Article
- Multi-Omics Analysis Identifies Tryptophan Metabolism and Glycolysis as Potential Pathways Involved in the Protective Effects of Tormentic Acid Against Metabolic Associated Fatty Liver Disease.Pharmacology research & perspectives · 2026Article
- Advances in Lipid Metabolism Reprogramming in Hepatocellular Carcinoma.Journal of clinical and translational hepatology · 2026Review
- Article
- GLP-1 receptor agonist targets an AMPKα1-HIF1α-PFKFB3 metabolic vulnerability and enhances Lenvatinib response in hepatocellular carcinoma.NPJ precision oncology · 2026Article
- Targeting the HIF-1α/PPARγ axis with curcumin carbon dots to combat uranium nephrotoxicity.Journal of nanobiotechnology · 2026Article
- Targeting Pyruvate Kinase M2: Signal Transduction Pathways and Exploration of Cancer Therapeutic Strategies.The AAPS journal · 2026Review
- AFP Stimulates Glucose Metabolic Reprogramming Contributing to Hepatocellular Carcinoma Resist Sorafenib Through Activating PI3K/AKT Signalling Pathway.Journal of cellular and molecular medicine · 2026Article
- SETD1A Regulates Glycolysis and Senescence of Nucleus Pulposus Cells via H3K4me3-HELZ2/PPARα-HIF1α Axis to Drive Intervertebral Disc Degeneration.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Simvastatin Restores Cisplatin Sensitivity by Suppressing the Caveolin-1-Mediated PI3K/AKT Signaling Pathway in Cisplatin-Resistant Cervical Cancer Cells.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Simvastatin in liver diseases: therapeutic value and research advances.Clinical and experimental medicine · 2026Review
- Declined RTN3 stabilizes DHCR7 to induce cholesterol-dependent tumor progression and MEK inhibitors insensitivity in thyroid cancer.Cell death & disease · 2026Article
- Disengaging the Engine: Histone Deacetylases 1 and 2-Mediated Acetylation of Hexokinase-2 Regulates Energy Metabolism in Microglia Following Intracerebral Hemorrhage.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Cholesterol Metabolism-related Characteristics Predict Therapeutic Response and Survival in Esophageal Cancer.Journal of advanced research · 2026Article
- Macrophage-delivered Nifuroxazide reprograms immunosuppressive microenvironment and synergizes with oxaliplatin for enhanced anti-hepatocellular carcinoma therapy.Journal of nanobiotechnology · 2026Article
103 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundHepatocellular carcinoma (HCC) is a common primary malignant tumor which usually progresses to an advanced stage because of late diagnosis. Sorafenib (Sora) is a first line medicine for advanced stage HCC; however, it has been faced with enormous resistance. Simvastatin (Sim) is a cholesterol-lowering drug and has been reported to inhibit tumor growth. The present study aims to determine whether Sora and Sim co-treatment can improve Sora resistance in HCC.
methodsThe HCC cell line LM3 and an established Sora-resistant LM3 cell line (LM3-SR) were used to study the relationship between Sora resistance and aerobic glycolysis. Cell proliferation, apoptosis and glycolysis levels were analyzed by western blotting, flow cytometry analysis and biomedical tests. A xenograft model was also used to examine the effect of Sim in vivo. Detailed mechanistic studies were also undertaken by the use of activators and inhibitors, and lentivirus transfections.
resultsOur results demonstrated that the resistance to Sora was associated with enhanced aerobic glycolysis levels. Furthermore, LM3-SR cells were more sensitive to Sim than LM3 cells, suggesting that combined treatment with both Sora and Sim could enhance the sensitivity of LM3-SR cells to Sora. This finding may be due to the suppression of the HIF-1α/PPAR-γ/PKM2 axis.
conclusionsSimvastatin can inhibit the HIF-1α/PPAR-γ/PKM2 axis, by suppressing PKM2-mediated glycolysis, resulting in decreased proliferation and increased apoptosis in HCC cells, and re-sensitizing HCC cells to Sora.
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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.