ArticleInternational journal of molecular sciences2022
Metformin Enhances the Anti-Cancer Efficacy of Sorafenib via Suppressing MAPK/ERK/Stat3 Axis in Hepatocellular Carcinoma.
Article in International journal of molecular sciences, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.
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Who cites it
25 citing papers in PubMed, 1 synthesis or guideline pooled it, 30 citations in OpenAlex.
- The correlation between novel antidiabetic agents utilization and hepatocellular carcinoma incidence in type 2 diabetes patients: a network meta-analysis.European journal of clinical pharmacology · 2025Pooled it
- Combination of oxidative phosphorylation and platelet-derived growth factor inhibitors for the treatment of ovarian cancers.npj women's health · 2026Article
- Phenotypic Response Surfaces-Guided Optimization (PRS-OPT) of Propolis-Metformin-Regorafenib Combination Therapy for MASLD-Associated Hepatocellular Carcinoma.Oncology research · 2026Article
- ZNF529 up-regulation speeds up progression and induces tyrosine kinase inhibitor resistance in hepatocellular carcinoma.Journal of gastrointestinal oncology · 2025Article
- Kuwanon A Targeted YWHAB in Hepatocellular Carcinoma Cells to Inhibit the Raf/MEK/ERK Signaling Pathway.Cells · 2025Article
- Review
- Fasting in combination with the cocktail Sorafenib:Metformin blunts cellular plasticity and promotes liver cancer cell death via poly-metabolic exhaustion.Cellular oncology (Dordrecht, Netherlands) · 2025Article
- Traditional Chinese Medicine Monomers and Their Derivatives as a Promising Therapeutic Tool for Hepatocellular Carcinoma by Activation of Mitophagy.Drug design, development and therapy · 2025Review
- Advances in the Use of Metformin for Liver Disease.Current medicinal chemistry · 2025Review
- Metformin and its Nanoformulations in Cancer Prevention and Therapy.Current pharmaceutical design · 2025Review
- Building of CuOPharmaceutics · 2024Article
- Unveiling the impacts of metformin on hepatocellular carcinoma: A bioinformatic exploration in cell lines.Narra J · 2024Article
- LUCAT1-Mediated Competing Endogenous RNA (ceRNA) Network in Triple-Negative Breast Cancer.Cells · 2024Article
- Enhanced anticancer activity of silver doped zinc oxide magnetic nanocarrier loaded with sorafenib for hepatocellular carcinoma treatment.Scientific reports · 2024Article
- SOD1 inhibition enhances sorafenib efficacy in HBV-related hepatocellular carcinoma by modulating PI3K/Akt/mTOR pathway and ROS-mediated cell death.Journal of cellular and molecular medicine · 2024Article
- Metabolic Reprogramming in Thyroid Cancer.Endocrinology and metabolism (Seoul, Korea) · 2024Review
- TMEM9 promotes lung adenocarcinoma progression via activating the MEK/ERK/STAT3 pathway to induce VEGF expression.Cell death & disease · 2024Article
- Mechanistic Insights about Sorafenib-, Valproic Acid- and Metformin-Induced Cell Death in Hepatocellular Carcinoma.International journal of molecular sciences · 2024Review
- Prognostic role of metformin in diabetes mellitus type 2 patients with hepatocellular carcinoma: A systematic review and meta-analysis.World journal of diabetes · 2023Article
- Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hepatocellular carcinoma (HCC) incidence, as well as related mortality, has been steadily increasing in the USA and across the globe, partly due to the lack of effective therapeutic options for advanced HCC. Though sorafenib is considered standard-of-care for advanced HCC, it only improves median survival by a few months when compared to placebo. Sorafenib is also associated with several unpleasant side effects that often lead to early abatement of therapy. Here, we investigate whether a combination regimen including low-dose sorafenib and a non-toxic dose of anti-diabetic drug metformin can achieve effective inhibition of HCC. Indeed, combining metformin with low-dose sorafenib inhibited growth, proliferation, migration, and invasion potential of HCC cells. We observed a 5.3- and 1.9-fold increase in sub-G1 population in the combination treatment compared to sorafenib alone. We found that the combination of metformin enhanced the efficacy of sorafenib and inhibited the MAPK/ERK/Stat3 axis. Our in vivo studies corroborated the in vitro findings, and mice harboring HepG2-derived tumors showed effective tumor reduction upon treatment with low-dose sorafenib and metformin combination. This work sheds light on a therapeutic strategy aiming to augment sorafenib efficacy or dose-de-escalation that may prove beneficial in circumventing sorafenib resistance as well as minimizing related side effects.
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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.