ArticlePloS one2014
AMP-activated protein kinase suppresses the in vitro and in vivo proliferation of hepatocellular carcinoma.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers, 2 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
46 citing papers in PubMed, 2 syntheses or guidelines pooled it, 72 citations in OpenAlex.
- Pooled it
- Anti-tumor effects of metformin in animal models of hepatocellular carcinoma: a systematic review and meta-analysis.PloS one · 2015Pooled it
- Research Progress on the Molecular Mechanism of Metformin Regulating AMPK Signaling Pathway in Inhibiting Liver Cancer.OncoTargets and therapy · 2026Review
- Navigating the Labyrinth of Hepatocellular Carcinoma: Leveraging AI/ML for Precision Oncology.Oncology research · 2026Review
- AMPK-Dependent Epigenetic Regulation of Metabolism Mediates the Anti-Cancer Action of Pterostilbene in Hepatocellular Carcinoma.Molecular nutrition & food research · 2025Article
- mTOR inhibition triggers mitochondrial fragmentation in cardiomyocytes through proteosome-dependent prohibitin degradation and OPA-1 cleavage.Cell communication and signaling : CCS · 2025Article
- Research Progress of Liver Cancer Recurrence Based on Energy Metabolism of Liver Cancer Stem Cells.Journal of hepatocellular carcinoma · 2025Review
- Targeting Oxidative Phosphorylation with a Novel Thiophene Carboxamide Increases the Efficacy of Imatinib against Leukemic Stem Cells in Chronic Myeloid Leukemia.International journal of molecular sciences · 2024Article
- Alpha lipoic acid diminishes migration and invasion in hepatocellular carcinoma cells through an AMPK-p53 axis.Scientific reports · 2024Article
- Plasma-activated medium exerts tumor-specific inhibitory effect on hepatocellular carcinoma via disruption of the salvage pathway.Journal of clinical biochemistry and nutrition · 2024Article
- Article
- Nanomaterials modulate tumor-associated macrophages for the treatment of digestive system tumors.Bioactive materials · 2024Review
- The role of metabolic reprogramming in liver cancer and its clinical perspectives.Frontiers in oncology · 2024Review
- Progestin-based pharmacotherapy in fertility preservation in early endometrial cancer.Frontiers in oncology · 2024Review
- Impact of AMPK on cervical carcinoma progression and metastasis.Cell death & disease · 2023Article
- The role of AMPK in cancer metabolism and its impact on the immunomodulation of the tumor microenvironment.Frontiers in immunology · 2023Review
- Isatin Counteracts Diethylnitrosamine/2-Acetylaminofluorene-Induced Hepatocarcinogenesis in Male Wistar Rats by Upregulating Anti-Inflammatory, Antioxidant, and Detoxification Pathways.Antioxidants (Basel, Switzerland) · 2022Article
- Systems Pharmacology-Based Strategy to Investigate the Mechanism of Ruangan Lidan Decoction for Treatment of Hepatocellular Carcinoma.Computational and mathematical methods in medicine · 2022Article
- Identification of Energy Metabolism-Related Gene Signatures From scRNA-Seq Data to Predict the Prognosis of Liver Cancer Patients.Frontiers in cell and developmental biology · 2022Article
- WWP1 inactivation enhances efficacy of PI3K inhibitors while suppressing their toxicities in breast cancer models.The Journal of clinical investigation · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
AMP-activated protein kinase (AMPK) is a central metabolic sensor and plays an important role in regulating glucose, lipid and cholesterol metabolism. Therefore, AMPK is a key therapeutic target in diabetes. Recent pilot studies have suggested that diabetes drugs may reduce the risk of cancer by affecting the AMPK pathway. However, the association between AMPK and the proliferation of hepatocellular carcinoma (HCC) is unknown. In this study, we investigated the relationship between AMPK activity and the proliferation of HCC in cell lines, nude mice and human clinic samples. We first investigated the relationship between AMPK activity and cell proliferation in two HCC cell lines, PLC/PRF/5 and HepG2, by two AMPK activators, 5-aminoimidazole-4-carboxamide-1-h-D-ribofuranoside (AICAR) and metformain. AICAR and metformin treatment significantly inhibited the proliferation of HCC cells and induced cell cycle arrest at G1-S checkpoint. We then observed that metformin abrogated the growth of HCC xenografts in nude mice. The clinical pathology of AMPK activity in HCC, including cell proliferation, differential grade, tumor size and microvessel density, was studied by using 30 clinical tissue samples. In HCC tissue samples, phosphorylated AMPK was expressed mainly in cytoplasm. AMPK activity decreased significantly in HCC in comparison with paracancerous liver tissues (P<0.05). AMPK activity was negatively correlated with the level of Ki-67 (a marker of cell proliferation), differential degradation and tumor size (P<0.05), but not with microvessel density, hemorrhage or necrosis in HCC. Our findings suggest that AMPK activity inhibits the proliferation of HCC and AMPK might be an effective target for prevention and treatment of HCC.
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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.