ArticleInternational journal of molecular sciences2016
Up-Regulation of PAI-1 and Down-Regulation of uPA Are Involved in Suppression of Invasiveness and Motility of Hepatocellular Carcinoma Cells by a Natural Compound Berberine.
Article in International journal of molecular sciences, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
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15 citing papers in PubMed, 1 synthesis or guideline pooled it, 43 citations in OpenAlex.
- A comprehensive review of phytoconstituents in liver cancer prevention and treatment: targeting insights into molecular signaling pathways.Medical oncology (Northwood, London, England) · 2024Pooled it
- Hypericin Nanoparticles-Associated Photodynamic Therapy Modulates the Biological Behavior of Hepatocellular Carcinoma by SERPINE1.International journal of nanomedicine · 2025Article
- Article
- The fibrinolytic system enables the onset ofScience advances · 2021Article
- Berberine inhibited metastasis through miR-145/MMP16 axis in vitro.Journal of ovarian research · 2021Article
- Aberrant Factors of Fibrinolysis and Coagulation in Pancreatic Cancer.OncoTargets and therapy · 2021Review
- Exploring the active mechanism of berberine against HCC by systematic pharmacology and experimental validation.Molecular medicine reports · 2019Article
- hERG1 is involved in the pathophysiological process and inhibited by berberine in SKOV3 cells.Oncology letters · 2019Article
- The Role of AMP-Activated Protein Kinase as a Potential Target of Treatment of Hepatocellular Carcinoma.Cancers · 2019Review
- Naturally occurring anti-cancer compounds: shining from Chinese herbal medicine.Chinese medicine · 2019Review
- Berberine Inhibits Human Melanoma A375.S2 Cell Migration and Invasion via Affecting the FAK, uPA, and NF-κB Signaling Pathways and Inhibits PLX4032 Resistant A375.S2 Cell Migration In Vitro.Molecules (Basel, Switzerland) · 2018Article
- Identification of Biological Targets of Therapeutic Intervention for Hepatocellular Carcinoma by Integrated Bioinformatical Analysis.Medical science monitor : international medical journal of experimental and clinical research · 2018Article
- Regulation of Akt/FoxO3a/Skp2 Axis Is Critically Involved in Berberine-Induced Cell Cycle Arrest in Hepatocellular Carcinoma Cells.International journal of molecular sciences · 2018Article
- Recent Advances in Herbal Medicines for Digestive System Malignancies.Frontiers in pharmacology · 2018Review
- Review
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related death and its prognosis remains poor due to the high risk of tumor recurrence and metastasis. Berberine (BBR) is a natural compound derived from some medicinal plants, and accumulating evidence has shown its potent anti-tumor activity with diverse action on tumor cells, including inducing cancer cell death and blocking cell cycle and migration. Molecular targets of berberine involved in its inhibitory effect on the invasiveness remains not yet clear. In this study, we identified that berberine exhibits a potent inhibition on the invasion and migration of HCC cells. This was accompanied by a dose-dependent down-regulation of expression of Cyclooxygenase-2 (COX-2), nuclear factor kappa B (NF-κB), urokinase-type plasminogen activator (uPA) and matrix metalloproteinase (MMP)-9 in berberine-treated HCC cells. Furthermore, berberine inactivated p38 and Erk1/2 signaling pathway in HCC cells. Primarily, this may be attributed to the up-regulation of plasminogen activator inhibitor-1 (PAI-1), a tumor suppressor that can antagonize uPA receptor and down-regulation of uPA. Blockade of uPA receptor-associated pathways leads to reduced invasiveness and motility of berberine-treated HCC cells. In conclusion, our findings identified for the first time that inactivation of uPA receptor by up-regulation of PAI-1 and down-regulation of uPA is involved in the inhibitory effect of berberine on HCC cell invasion and migration.
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