ArticleJournal of Cancer2022
Combination of Metformin and Sorafenib Induces Ferroptosis of Hepatocellular Carcinoma Through p62-Keap1-Nrf2 Pathway.
Article in Journal of Cancer, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 52 citations in OpenAlex.
- Metformin Inhibits Ferroptotic Cell Death by Suppressing Cysteine Deprivation-Induced Mitochondrial Dysfunction.Pharmacology research & perspectives · 2026Article
- NRF2-mediated immune evasion and ferroptosis resistance in hepatocellular carcinoma: implications for immune checkpoint inhibitor response.Journal of liver cancer · 2026Article
- TrxR Inhibition and Nrf2-FOXO3 Modulation by Repurposed Drugs: A Redox Strategy to Reverse Cancer Multidrug Resistance.Drug development research · 2026Review
- Context-Dependent Modulation of Ferroptosis by Metformin: Mechanisms, Therapeutic Implications and Open Questions.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Nrf2 signaling pathway and its molecular regulatory mechanism.Journal of Zhejiang University. Science. B · 2026Review
- Enocyanin Synergistically Enhances Sorafenib Sensitivity in Hepatocellular Carcinoma via Ferroptosis Induction Associated with p62/Keap1/Nrf2/HO-1 Pathway Inhibition.Current issues in molecular biology · 2026Article
- Combination of sodium pentaborate pentahydrate, curcumin and piperine treatment induces ferroptosis in hepatocellular carcinoma cells by regulating iron homeostasis and ROS activity in vitro.Medical oncology (Northwood, London, England) · 2026Article
- The ferroptosis-ncRNA-exosome triad: key orchestrators in cancer immunopathogenesis.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- The NRF2 signaling pathway in hepatocellular carcinoma: dual roles, epigenetic reprogramming, and therapeutic opportunities in metabolic vulnerability.Frontiers in oncology · 2026Review
- CUL2 confers ferroptosis resistance in pancreatic cancer by disrupting KEAP1-mediated NRF2 degradation.Cancer cell international · 2025Article
- Deactivation of CK1α enhances the anti-cancer effects of salinomycin in colorectal cancer HCT116 cells.Biochemistry and biophysics reports · 2025Article
- Targeting ferroptosis by noncoding RNAs as a novel therapeutic strategy for hepatocellular carcinoma.Discover oncology · 2025Review
- Ferroptosis and cancer: when iron turns against tumors.Cellular and molecular life sciences : CMLS · 2025Review
- Mechanisms of ferroptosis in primary hepatocellular carcinoma and progress of artificial intelligence-based predictive modeling in hepatocellular carcinoma.World journal of gastroenterology · 2025Review
- The advantages and challenges of sorafenib combination therapy: Drug resistance, toxicity and future directions (Review).Oncology letters · 2025Review
- Roles of the Keap1/Nrf2 pathway and mitophagy in liver diseases.Journal of Zhejiang University. Science. B · 2025Review
- MiR-124 Delivered by Extracellular Vesicles from Mesenchymal Stem Cell Exerts Neuroprotective Effects by Stabilizing the p62-Keap1-Nrf2 Pathway after Spinal Cord Injury in Rats.Molecular neurobiology · 2025Article
- Ferroptosis in Gastrointestinal Diseases: A New Frontier in Pathogenesis and Therapy.Journal of clinical medicine · 2025Review
- Metformin Enhances the Chemosensitivity of Gastric Cancer to Cisplatin by Downregulating Nrf2 Level.Analytical cellular pathology (Amsterdam) · 2025Article
- Advances in the Use of Metformin for Liver Disease.Current medicinal chemistry · 2025Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hepatocellular carcinoma (HCC) is one of the most lethal cancers in the world. Sorafenib is the first small-molecule multi-kinase inhibitors approved by FDA for treatment of advanced HCC. Metformin has been demonstrated to have benefit for preventing cancer progression. In human recurrent HCCs, NF-E2-related factor 2 (Nrf2) was overexpressed and associated with poor survival. Nrf2 related signaling pathway plays central role to mediate cellular resistance to sorafenib through protecting HCC cells from ferroptosis. The effect of Combination treatment for HCC cells and the intrinsic mechanism have not been reported. In this study, metformin augmented the anti-tumor effect of sorafenib for HCC through ferroptosis induction by inhibiting Nrf2 related pathway. Based on the results of Nrf2 knockdown and p62 knockdown study, the combination of sorafenib and metformin suppressed proliferation of HCC cells through p62-Keap1-Nrf2/HO1 signaling way. Size of xenografts treated with the combination of sorafenib and metformin was smaller than other groups
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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.