ArticleInternational journal of endocrinology2019
Metformin Counteracts HCC Progression and Metastasis Enhancing KLF6/p21 Expression and Downregulating the IGF Axis.
Article in International journal of endocrinology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 33 citations in OpenAlex.
- AMPK-Mediated Lipid Metabolic Reprogramming in Cancer: From Mechanisms to Targeted Therapies.Cell biochemistry and function · 2026Review
- From kidney to liver: Are sodium-glucose cotransporter-2 inhibitors emerging as metabolic disease modifiers?World journal of nephrology · 2026Article
- AI-aided identification of dual-purpose therapeutic targets PRPF19 and MAPK9 in hepatocellular carcinoma and cellular senescence.npj aging · 2025Article
- Identification of potential oncogenic miRNA clusters with a special focus on miR-106b/25 cluster-regulated networks and their clinical utility in hepatocellular carcinoma.Discover oncology · 2025Article
- Role of cellular senescence in hepatic diseases (Review).International journal of molecular medicine · 2025Review
- Deciphering the heterogeneity of epithelial cells in pancreatic ductal adenocarcinoma: implications for metastasis and immune evasion.World journal of surgical oncology · 2025Article
- Metformin: A Dual-Role Player in Cancer Treatment and Prevention.International journal of molecular sciences · 2024Review
- Identification of glucose-independent and reversible metabolic pathways associated with anti-proliferative effect of metformin in liver cancer cells.Metabolomics : Official journal of the Metabolomic Society · 2024Article
- Use of Metformin and Survival in Patients with Hepatocellular Carcinoma (HCC) Undergoing Liver Directed Therapy: Analysis of a Nationwide Cancer Registry.Cardiovascular and interventional radiology · 2023Article
- Review
- Current trends and future prospects of drug repositioning in gastrointestinal oncology.Frontiers in pharmacology · 2023Review
- Pathogenesis and Current Treatment Strategies of Hepatocellular Carcinoma.Biomedicines · 2022Review
- Role of metformin in the diagnosis, prevention, and treatment of hepatocellular carcinoma.Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2022Article
- Identification of m6A- and ferroptosis-related lncRNA signature for predicting immune efficacy in hepatocellular carcinoma.Frontiers in immunology · 2022Article
- Antitumor Effects and Mechanisms of Metabolic Syndrome Medications on Hepatocellular Carcinoma.Journal of hepatocellular carcinoma · 2022Review
- The role of AMPK/mTOR signaling pathway in anticancer activity of metformin.Physiological research · 2021Review
- Metformin and Everolimus: A Promising Combination for Neuroendocrine Tumors Treatment.Cancers · 2020Article
- L-Carnitine counteracts in vitro fructose-induced hepatic steatosis through targeting oxidative stress markers.Journal of endocrinological investigation · 2020Article
- Combination of aloin and metformin enhances the antitumor effect by inhibiting the growth and invasion and inducing apoptosis and autophagy in hepatocellular carcinoma through PI3K/AKT/mTOR pathway.Cancer medicine · 2020Article
- Metformin Promotes Beclin1-Dependent Autophagy to Inhibit the Progression of Gastric Cancer.OncoTargets and therapy · 2020Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND
aimsHepatocellular carcinoma (HCC) is the common tumor of the liver. Unfortunately, most HCC seem to be resistant to conventional chemotherapy and radiotherapy. The poor efficacy of antitumor agents is also due, at least in part, to the inefficient drug delivery and metabolism exerted by the steatotic/cirrhotic liver that hosts the tumor. Thus, novel approaches in chemotherapy may be needed to improve the survival rate in patients with HCC. Metformin (METF) has been found to lower HCC risk; however, the mechanisms by which METF performs its anticancer activity are not completely elucidated. Previous studies have showed METF action on growth inhibition in the liver in a dose/time-dependent manner and its antitumor role by targeting multiple pathways. We investigated molecular effects of METF in an MATERIALS AND
methodsHepG2 cells were treated with METF (400
resultsBy assessing HepG2 cell viability, METF significantly decreased growth cell capacity raising KLF6/p21 protein content. Moreover, METF ameliorated the cancer microenvironment reducing cellular lipid drop accumulation and promoting AMPK activity. The overexpression of IGF-II molecule and the IGF-I receptor that plays a main role in HCC progression was counteracted by METF. Furthermore, the protein content of HCC principal tumor markers, CK19 and OPN, linked to the metastasis process was significantly reduced by METF stimulus.
conclusionOur data show that METF could suppress HepG2 proliferation, through induction of cell cycle arrest at the G0/G1 phase. In addition, METF effect on the cancer microenvironment and on the IGF axis leads to the development of new METF therapeutic use in HCC treatment.
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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.