ArticleProceedings of the National Academy of Sciences of the United States of America2015
Sorafenib and its derivative SC-1 exhibit antifibrotic effects through signal transducer and activator of transcription 3 inhibition.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed.
- Saikosaponin b1 Attenuates Liver Fibrosis by Blocking STAT3/Gli1 Interaction and Inducing Gli1 Degradation.Exploration (Beijing, China) · 2025Article
- NCOA5 induces sorafenib resistance in hepatocellular carcinoma by inhibiting ferroptosis.Cell death discovery · 2025Article
- Gout drives metabolic dysfunction-associated steatotic liver disease through gut microbiota and inflammatory mediators.Scientific reports · 2025Article
- JAK2V617F-dependent down regulation of SHP-1 expression participates in the selection of myeloproliferative neoplasm cells in the presence of TGF-β.Journal of cellular and molecular medicine · 2024Article
- Lactucin reverses liver fibrosis by inhibiting TGF-β1/STAT3 signaling pathway and regulating short-chain fatty acids metabolism.Scientific reports · 2024Article
- Recent Advances in Research on Active Compounds Against Hepatic Fibrosis.Current medicinal chemistry · 2024Review
- Pirfenidone ameliorates liver steatosis by targeting the STAT3-SCD1 axis.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2023Article
- Targeting pathogenic macrophages by the application of SHP-1 agonists reduces inflammation and alleviates pulmonary fibrosis.Cell death & disease · 2023Article
- Biomimetic nanoparticles drive the mechanism understanding of shear-wave elasticity stiffness in triple negative breast cancers to predict clinical treatment.Bioactive materials · 2023Article
- Advances in the Development of Small Molecule Antivirals against Equine Encephalitic Viruses.Viruses · 2023Review
- Spatial molecular and cellular determinants of STAT3 activation in liver fibrosis progression in non-alcoholic fatty liver disease.JHEP reports : innovation in hepatology · 2023Article
- Beneficial effects of ginkgetin on improving nonalcoholic steatohepatitis characterized by bulk and single-cell RNA sequencing analysis.Frontiers in pharmacology · 2023Article
- SHP-1/STAT3-Signaling-Axis-Regulated Coupling between BECN1 and SLC7A11 Contributes to Sorafenib-Induced Ferroptosis in Hepatocellular Carcinoma.International journal of molecular sciences · 2022Article
- Sorafenib attenuates liver fibrosis by triggering hepatic stellate cell ferroptosis via HIF-1α/SLC7A11 pathway.Cell proliferation · 2022Article
- Lipophilic Constituents inFrontiers in pharmacology · 2022Article
- Kinase Inhibitor Library Screening Identifies the Cancer Therapeutic Sorafenib and Structurally Similar Compounds as Strong Inhibitors of the Fungal PathogenAntibiotics (Basel, Switzerland) · 2021Article
- Article
- HJC0416 Attenuates Fibrogenesis in Activated Hepatic Stellate Cells via STAT3 and NF-κB Pathways.The Journal of surgical research · 2021Article
- Therapeutic targeting of STAT3 with small interference RNAs and antisense oligonucleotides embedded exosomes in liver fibrosis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
- Control of adipogenic commitment by a STAT3-VSTM2A axis.American journal of physiology. Endocrinology and metabolism · 2021Article
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Authors and funding
15 authors.
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Abstract
Signal transducer and activator of transcription 3 (STAT3) had been involved in liver fibrogenesis. We aimed to explore the antifibrotic activities of sorafenib and its derivative SC-1 (devoid of Raf kinase inhibition activity) both in vivo and in vitro with special focus on the STAT3 pathway in hepatic stellate cells (HSCs). The clinical role of STAT3 in chronic hepatitis B (CHB) was also investigated. Experimental fibrosis mouse models were established by thioacetamide injection and bile duct ligation in Balb/C mice and treated with sorafenib and SC-1. Rat and human HSCs were used for mechanistic investigations. Forty CHB patients were enrolled to quantify the hepatic phospho-STAT3 (p-STAT3) levels and correlated with liver fibrosis. Both sorafenib and SC-1 ameliorated liver fibrosis in vivo and promoted HSC apoptosis in vitro. p-STAT3 and downstream signals were down-regulated after sorafenib and SC-1 treatment in HSC. STAT3 overexpression in HSC enhanced cell proliferation and undermined the apoptotic effects of sorafenib and SC-1, whereas STAT3-specific inhibition promoted HSC apoptosis. Sorafenib and SC-1 activated Src-homology protein tyrosine phosphatase-1 (SHP-1) and STAT3 inhibition followed. Of particular interest, in CHB patients with advanced liver fibrosis, p-STAT3 in HSC was significantly overexpressed and positively correlated with the severity of liver fibrosis and plasma IL-6 levels. In conclusion, sorafenib and SC-1 ameliorate liver fibrosis through STAT3 inhibition in HSC and STAT3 may potentially serve as a promising fibrotic biomarker and target in liver fibrosis. SHP-1 phosphatase-directed STAT3 inhibition may represent a previously unidentified strategy for antifibrotic drug discovery.
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