ArticleHPB : the official journal of the International Hepato Pancreato Biliary Association2011
Leptin inhibits hepatocellular carcinoma proliferation via p38-MAPK-dependent signalling.
Article in HPB : the official journal of the International Hepato Pancreato Biliary Association, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
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Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 33 citations in OpenAlex.
- A meta-analysis of reference values of leptin concentration in healthy postmenopausal women.PloS one · 2013Pooled it
- Advances in targeting p38 MAPK for cancer therapy: insights from molecular pharmacology and medicinal chemistry.Molecular diversity · 2026Review
- Article
- Leptin increases chemosensitivity by inhibitingJournal of gastrointestinal oncology · 2024Article
- Role of Different Variants of Leptin Receptor in Human Adrenal Tumor Types.International journal of molecular sciences · 2024Article
- Impact of obesity‑associated myeloid‑derived suppressor cells on cancer risk and progression (Review).International journal of oncology · 2024Review
- Obesity paradox in uveal melanoma: high body mass index is associated with low metastatic risk.The British journal of ophthalmology · 2024Article
- [Associations of circulating leptin levels with colorectal adenoma and colorectal cancer: a case-control and Mendelian randomization study].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2023Article
- Recent Advances in the Knowledge of the Mechanisms of Leptin Physiology and Actions in Neurological and Metabolic Pathologies.International journal of molecular sciences · 2023Review
- Leptin, Both Bad and Good Actor in Cancer.Biomolecules · 2021Review
- Leptin and Cancer: Updated Functional Roles in Carcinogenesis, Therapeutic Niches, and Developments.International journal of molecular sciences · 2021Review
- The Adipokine Component in the Molecular Regulation of Cancer Cell Survival, Proliferation and Metastasis.Pathology oncology research : POR · 2021Review
- IL-6/STAT3 Is a Promising Therapeutic Target for Hepatocellular Carcinoma.Frontiers in oncology · 2021Review
- Unraveling the Role of Leptin in Liver Function and Its Relationship with Liver Diseases.International journal of molecular sciences · 2020Review
- Significance of 5-International journal of molecular sciences · 2020Review
- Leptin signaling axis specifically associates with clinical prognosis and is multifunctional in regulating cancer progression.Oncotarget · 2018Review
- Hepatoma cell-derived leptin downregulates the immunosuppressive function of regulatory T-cells to enhance the anti-tumor activity of CD8+ T-cells.Immunology and cell biology · 2016Article
- Leptin Promotes cPLA₂ Gene Expression through Activation of the MAPK/NF-κB/p300 Cascade.International journal of molecular sciences · 2015Article
- Role of biomarkers in the prediction and diagnosis of hepatocellular carcinoma.World journal of hepatology · 2015Review
- High-saturate-fat diet delays initiation of diethylnitrosamine-induced hepatocellular carcinoma.BMC gastroenterology · 2014Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectivesObesity is a significant risk factor for many liver diseases, including hepatocellular carcinoma (HCC). Leptin has been identified as a central mediator of factors that regulate energy intake and expenditure, including appetite, metabolism and fat storage. The role of leptin in the initiation, development and progression of HCC remains poorly understood. The aims of this study were to determine the effect(s) of leptin on HCC cell proliferation and to identify potential signalling mechanism(s) by which leptin exerts these effects.
methodsRat H4IIE HCC cells and H4IIE-derived HCC tumours were analysed for leptin receptor (LR) expression. H4IIE cells were treated with leptin (0-100 ng/ml) in the absence or presence of pharmacological inhibitors of p42/p44 mitogen-activated protein kinase (MAPK) (PD98059), p38-MAPK (SB202190) or Janus kinase-signal transducers and activators of transcription (JAK-STAT) (AG490; 10 µM) signalling. Cell proliferation was determined and signal pathway activity analysed.
resultsImmunohistochemistry identified increased LR expression in HCC in human tissue. Leptin did not significantly affect H4IIE cell numbers in serum-depleted (0.1% [v/v] foetal bovine serum [FBS]) medium. However, leptin significantly inhibited serum-stimulated (1.0% [v/v] FBS) H4IIE proliferation. Immunoblot analysis demonstrated that leptin significantly activated p42/p44-MAPK, p38-MAPK and STAT3 signalling in a time-dependent manner. Pretreatment of H4IIE cells with SB202190 abrogated leptin-dependent inhibition of H4IIE proliferation, an effect not observed in cells pretreated with PD98059 or AG490.
conclusionsLeptin inhibits HCC cell growth in vitro via a p38-MAPK-dependent signalling pathway. Identifying similar effects on tumour growth in vivo may provide an attractive therapeutic target for slowing HCC progression.
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