ArticleWorld journal of gastroenterology2011
Sorafenib inhibits growth and metastasis of hepatocellular carcinoma by blocking STAT3.
Article in World journal of gastroenterology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 86 citations in OpenAlex.
- First-in-human trial of a STAT3 decoy oligonucleotide in head and neck tumors: implications for cancer therapy.Cancer discovery · 2012Trial
- IntravChip: a vascularized and perfused microfluidic model of the primary tumor microenvironment to collect intravasated tumor cells.Biofabrication · 2026Article
- IntravChip: a vascularized and perfused microfluidic model of the primary tumor microenvironment to collect intravasated tumor cells.bioRxiv : the preprint server for biology · 2026Article
- Coordinated gene expression within sustained STAT3-associated chromatin conformations contributes to hepatocellular carcinoma progression.Cancer communications (London, England) · 2025Article
- Exploring the Updated Roles of Ferroptosis in Liver Diseases: Mechanisms, Regulators, and Therapeutic Implications.Cell biochemistry and biophysics · 2025Review
- Key Role of STAT3 in Osteoarthritis: From Pathogenic Mechanisms to Targeted Therapy.International journal of nanomedicine · 2025Review
- Signaling pathways in liver cancer: pathogenesis and targeted therapy.Molecular biomedicine · 2024Review
- Article
- Emerging Potential Mechanism and Therapeutic Target of Ferroptosis in PDAC: A Promising Future.International journal of molecular sciences · 2022Review
- Modulation of the tumour microenvironment in hepatocellular carcinoma by tyrosine kinase inhibitors: from modulation to combination therapy targeting the microenvironment.Cancer cell international · 2022Review
- Therapeutic efficacy of aJournal of traditional and complementary medicine · 2021Article
- A combination of sorafenib and radiotherapy reduces NF-κB activity and growth of hepatocellular carcinoma in an orthotopic mouse model.Oncology letters · 2021Article
- Inflammatory microenvironment of fibrotic liver promotes hepatocellular carcinoma growth, metastasis and sorafenib resistance through STAT3 activation.Journal of cellular and molecular medicine · 2021Article
- Sorafenib and CuB exert synergistic antitumor effects against hepatocellular carcinoma cells via inhibition of STAT3 phosphorylation.FEBS open bio · 2021Article
- The Effects of Capsaicin on Gastrointestinal Cancers.Molecules (Basel, Switzerland) · 2020Review
- Review
- Bear Bile Powder Inhibits Growth of Hepatocellular Carcinoma via Suppressing STAT3 Signaling Pathway in Mice.Chinese journal of integrative medicine · 2020Article
- MEK inhibition enhances the response to tyrosine kinase inhibitors in acute myeloid leukemia.Scientific reports · 2019Article
- Inhibition of murine hepatoma tumor growth by cryptotanshinone involves TLR7-dependent activation of macrophages and induction of adaptive antitumor immune defenses.Cancer immunology, immunotherapy : CII · 2019Article
- Role of microRNAs in the development of hepatocellular carcinoma and drug resistance.Frontiers in bioscience (Landmark edition) · 2019Review
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
aimTo investigate the inhibitory role and the underlying mechanisms of sorafenib on signal transducer and activator of transcription 3 (STAT3) activity in hepatocellular carcinoma (HCC).
methodsHuman and rat HCC cell lines were treated with sorafenib. Proliferation and STAT3 dephosphorylation were assessed. Potential molecular mechanisms of STAT3 pathway inhibition by sorafenib were evaluated. In vivo antitumor action and STAT3 inhibition were investigated in an immunocompetent orthotopic rat HCC model.
resultsSorafenib decreased STAT3 phosphorylation at the tyrosine and serine residues (Y705 and S727), but did not affect Janus kinase 2 (JAK2) and phospha-tase shatterproof 2 (SHP2), which is associated with growth inhibition in HCC cells. Dephosphorylation of S727 was associated with attenuated extracellular signal-regulated kinase (ERK) phosphorylation, similar to the effects of a mitogen-activated protein kinase (MEK) inhibitor U0126, suggesting that sorafenib induced S727 dephosphorylation by inhibiting MEK/ERK signaling. Meanwhile, sorafenib could also inhibit Akt phosphorylation, and both the phosphatidylinositol-3-kinase (PI3K) inhibitor LY294002 and Akt knockdown resulted in Y705 dephosphorylation, indicating that Y705 dephosphorylation by sorafenib was mediated by inhibiting the PI3K/Akt pathway. Finally, in the rat HCC model, sorafenib significantly inhibited STAT3 activity, reducing tumor growth and metastasis.
conclusionSorafenib inhibits growth and metastasis of HCC in part by blocking the MEK/ERK/STAT3 and PI3K/Akt/STAT3 signaling pathways, but independent of JAK2 and SHP2 activation.
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