ArticleCancer science2016
Metformin inhibits estrogen-dependent endometrial cancer cell growth by activating the AMPK-FOXO1 signal pathway.
Article in Cancer science, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 50 citations in OpenAlex.
- Prospective Randomized Biomarker Study of Metformin and Lifestyle Intervention for Prevention in Obese Women at Increased Risk for Endometrial Cancer.Cancer prevention research (Philadelphia, Pa.) · 2018Trial
- Efficacy of combined metformin plus progestin therapy versus progestin monotherapy in endometrial hyperplasia: a randomized clinical trial.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- MPT0E028, a pan-HDAC inhibitor, ameliorates bleomycin-induced pulmonary fibrosis by promoting AT2-to-AT1 differentiation through the ATM/AMPK/FoxO1 pathway.Journal of biomedical science · 2026Article
- Metformin Reverses Progesterone Resistance in Endometrial Cancer by Targeting the AMPK-FOXO1-CALB2 Pathway.Current medicinal chemistry · 2026Article
- FOXO1 phosphorylation as a context-dependent molecular switch in cancer: from mechanisms to precision therapy.World journal of surgical oncology · 2025Review
- Investigation of the mechanism by which FOXJ2 inhibits proliferation, metastasis and cell cycle progression of ovarian cancer cells through the PI3K/AKT signaling pathway.European journal of medical research · 2025Article
- Estrogen Receptor Is Required for Metformin-Induced Apoptosis in Breast Cancer Cells Under Hyperglycemic Conditions.Breast cancer : basic and clinical research · 2024Article
- Impact of Sex and Gender on Clinical Management of Patients with Advanced Chronic Liver Disease and Type 2 Diabetes.Journal of personalized medicine · 2023Review
- Action Mechanism of Metformin and Its Application in Hematological Malignancy Treatments: A Review.Biomolecules · 2023Review
- Phosphoproteomics Reveals the AMPK Substrate Network in Response to DNA Damage and Histone Acetylation.Genomics, proteomics & bioinformatics · 2022Article
- Article
- Metformin: Sex/Gender Differences in Its Uses and Effects-Narrative Review.Medicina (Kaunas, Lithuania) · 2022Review
- Metformin Intervention-A Panacea for Cancer Treatment?Cancers · 2022Review
- PPARα agonist fenofibrate relieves acquired resistance to gefitinib in non-small cell lung cancer by promoting apoptosis via PPARα/AMPK/AKT/FoxO1 pathway.Acta pharmacologica Sinica · 2022Article
- Receptor of Advanced Glycation End Products Deficiency Attenuates Cisplatin-Induced Acute Nephrotoxicity by Inhibiting Apoptosis, Inflammation and Restoring Fatty Acid Oxidation.Frontiers in pharmacology · 2022Article
- Effects of Forkhead box O1 on lipopolysaccharide-induced mitochondrial dysfunction in human cervical squamous carcinoma SiHa cells.Oncology letters · 2021Article
- PHLPP1/Nrf2-Mdm2 axis induces renal apoptosis via influencing nucleo-cytoplasmic shuttling of FoxO1 during diabetic nephropathy.Molecular and cellular biochemistry · 2021Article
- Article
- Forkhead Box Protein O1: Functional Diversity and Post-Translational Modification, a New Therapeutic Target?Drug design, development and therapy · 2021Review
- Dual anticancer role of metformin: an old drug regulating AMPK dependent/independent pathways in metabolic, oncogenic/tumorsuppresing and immunity context.American journal of cancer research · 2021Review
Corrections and comments
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Authors and funding
15 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Metformin is an oral biguanide commonly used for treating type II diabetes and has recently been reported to possess antiproliferative properties that can be exploited for the prevention and treatment of a variety of cancers. The mechanisms underlying this effect have not been fully elucidated. Our study shows a marked loss of AMP-activated protein kinase (AMPK) phosphorylation and nuclear human Forkhead box O1 (FOXO1) protein in estrogen-dependent endometrial cancer (EC) tumors compared to normal control endometrium. Metformin treatment suppressed EC cell growth in a time-dependent manner in vitro; this effect was cancelled by cotreatment with an AMPK inhibitor, compound C. Metformin decreased FOXO1 phosphorylation and increased FOXO1 nuclear localization in Ishikawa and HEC-1B cells, with non-significant increase in FOXO1 mRNA expression. Moreover, compound C blocked the metformin-induced changes of FOXO1 and its phosphorylation protein, suggesting that metformin upregulated FOXO1 activity by AMPK activation. Similar results were obtained after treatment with insulin. In addition, transfection with siRNA for FOXO1 cancelled metformin-inhibited cell growth, indicating that FOXO1 mediated metformin to inhibit EC cell proliferation. A xenograft mouse model further revealed that metformin suppressed HEC-1B tumor growth, accompanied by downregulated ki-67 and upregulated AMPK phosphorylation and nuclear FOXO1 protein. Taken together, these data provide a novel mechanism of antineoplastic effect for metformin through the regulation of FOXO1, and suggest that the AMPK-FOXO1 pathway may be a therapeutic target to the development of new antineoplastic drugs.
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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 OpenQuestion graph.