ArticleScientific reports2021
Metformin exerts anti-cancerogenic effects and reverses epithelial-to-mesenchymal transition trait in primary human intrahepatic cholangiocarcinoma cells.
Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.
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Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 30 citations in OpenAlex.
- Effects of Metformin on Risk and Prognosis of Biliary Tract Cancer: A Systematic Review and Meta-Analysis.Medicina (Kaunas, Lithuania) · 2023Pooled it
- Metformin use and the risk of liver cancer in a Swedish population-based cohort study.JNCI cancer spectrum · 2026Article
- Dose-dependent effects of Metformin on proliferation and odontogenic differentiation of dental pulp stem cells.BMC oral health · 2026Article
- Inhibition of Glutamate Dehydrogenase as a Potential Strategy to Modulate Intrahepatic Cholangiocarcinoma Cell Metabolism.Biomolecules · 2026Article
- Cholangiocarcinoma 2026: status quo, unmet needs and priorities.Nature reviews. Gastroenterology & hepatology · 2026Review
- Metformin Inhibits the Growth of Hypopharyngeal Squamous Cell Carcinoma of Fadu Cell and Down-Regulates LncAROD to Improve Prognosis.Anti-cancer agents in medicinal chemistry · 2026Article
- Research Progress on the Molecular Mechanism of Metformin Regulating AMPK Signaling Pathway in Inhibiting Liver Cancer.OncoTargets and therapy · 2026Review
- Association of metformin with risk of digestive tract cancers from a drug target mendelian randomization and cell experiments.Discover oncology · 2025Article
- Advances in the Use of Metformin for Liver Disease.Current medicinal chemistry · 2025Review
- The metabolic landscape of ovarian cancer stem cells: how do they survive?Frontiers in oncology · 2025Review
- Association between incretin-based drugs and risk of cholangiocarcinoma among patients with type 2 diabetes: A large population-based matched cohort study.Journal of clinical & translational endocrinology · 2024Article
- Metformin dampens the progression of cholangiofibrosis induced by thioacetamide using deep learning.Heliyon · 2024Article
- The Tumor Immune Microenvironment plays a Key Role in Driving the Progression of Cholangiocarcinoma.Current cancer drug targets · 2024Review
- Combination of metformin/efavirenz/fluoxetine exhibits profound anticancer activity via a cancer cell-specific ROS amplification.Cancer biology & therapy · 2023Article
- Metformin and empagliflozin modulate monoamine oxidase-related oxidative stress and improve vascular function in human mammary arteries.Molecular and cellular biochemistry · 2023Article
- The function, mechanisms, and clinical applications of metformin: potential drug, unlimited potentials.Archives of pharmacal research · 2023Review
- Therapeutic effects of dexamethasone-loaded hyaluronan nanogels in the experimental cholestasis.Drug delivery and translational research · 2022Article
- YAP1 activation and Hippo pathway signaling in the pathogenesis and treatment of intrahepatic cholangiocarcinoma.Advances in cancer research · 2022Review
- Epithelial-to-Mesenchymal Transition Is Not a Major Modulating Factor in the Cytotoxic Response to Natural Products in Cancer Cell Lines.Molecules (Basel, Switzerland) · 2021Article
- The Effects of NT-1044, a Novel AMPK Activator, on Endometrial Cancer Cell Proliferation, Apoptosis, Cell Stress andFrontiers in oncology · 2021Article
Corrections and comments
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Authors and funding
22 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Intrahepatic cholangiocarcinoma (iCCA) is a highly aggressive cancer with marked resistance to chemotherapeutics without therapies. The tumour microenvironment of iCCA is enriched of Cancer-Stem-Cells expressing Epithelial-to-Mesenchymal Transition (EMT) traits, being these features associated with aggressiveness and drug resistance. Treatment with the anti-diabetic drug Metformin, has been recently associated with reduced incidence of iCCA. We aimed to evaluate the anti-cancerogenic effects of Metformin in vitro and in vivo on primary cultures of human iCCA. Our results showed that Metformin inhibited cell proliferation and induced dose- and time-dependent apoptosis of iCCA. The migration and invasion of iCCA cells in an extracellular bio-matrix was also significantly reduced upon treatments. Metformin increased the AMPK and FOXO3 and induced phosphorylation of activating FOXO3 in iCCA cells. After 12 days of treatment, a marked decrease of mesenchymal and EMT genes and an increase of epithelial genes were observed. After 2 months of treatment, in order to simulate chronic administration, Cytokeratin-19 positive cells constituted the majority of cell cultures paralleled by decreased Vimentin protein expression. Subcutaneous injection of iCCA cells previously treated with Metformin, in Balb/c-nude mice failed to induce tumour development. In conclusion, Metformin reverts the mesenchymal and EMT traits in iCCA by activating AMPK-FOXO3 related pathways suggesting it might have therapeutic implications.
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