ArticleOncogene2009
The STAT3 inhibitor NSC 74859 is effective in hepatocellular cancers with disrupted TGF-beta signaling.
Article in Oncogene, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 111 papers, 2 of them syntheses that pooled it.
What it found
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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
111 citing papers in PubMed, 2 syntheses or guidelines pooled it, 211 citations in OpenAlex.
- Tumor growth suppression by inhibiting both autophagy and STAT3 signaling in HNSCC.Oncotarget · 2015Pooled it
- Pooled it
- A positive feedback loop between Periostin and TGFβ1 induces and maintains the stemness of hepatocellular carcinoma cells via AP-2α activation.Journal of experimental & clinical cancer research : CR · 2021Trial
- Mutual Exclusion Analysis Shows that DUSP9 Negatively Regulates PD-L1 Expression and Acts as a Target to Enhance Anti-PD-1 Efficacy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Transforming Growth Factor-β Signaling in Alcohol-Associated Liver Disease: A Multicellular Perspective.The American journal of pathology · 2026Review
- L-cystine alleviates necrotizing enterocolitis by regulating ferroptosis and Th17 cell differentiation via the IL-6/STAT3 pathway.Communications biology · 2025Article
- Coordinated gene expression within sustained STAT3-associated chromatin conformations contributes to hepatocellular carcinoma progression.Cancer communications (London, England) · 2025Article
- Non-receptor Type PTPases and their Role in Controlling Pathways Related to Diabetes and Liver Cancer Signalling.Current pharmaceutical biotechnology · 2025Review
- pSTAT3 activation ofProceedings of the National Academy of Sciences of the United States of America · 2024Article
- Prolactin is an Endogenous Antioxidant Factor in Astrocytes That Limits Oxidative Stress-Induced Astrocytic Cell Death via the STAT3/NRF2 Signaling Pathway.Neurochemical research · 2024Article
- Cancer stem cell-immune cell crosstalk in the tumor microenvironment for liver cancer progression.Frontiers of medicine · 2024Review
- Serine 727 phosphorylation is necessary to induce the STAT3-mediated transcription of LINC00184 in oesophageal squamous cell carcinoma.Molecular and cellular biochemistry · 2022Article
- A Soft Zwitterionic Hydrogel as Potential Coating on a Polyimide Surface to Reduce Foreign Body Reaction to Intraneural Electrodes.Molecules (Basel, Switzerland) · 2022Article
- Liver regeneration and inflammation: from fundamental science to clinical applications.Nature reviews. Molecular cell biology · 2021Review
- BMP9-ID1 signaling promotes EpCAM-positive cancer stem cell properties in hepatocellular carcinoma.Molecular oncology · 2021Article
- STAT3 and its targeting inhibitors in osteosarcoma.Cell proliferation · 2021Review
- Advances of Targeted Therapy for Hepatocellular Carcinoma.Frontiers in oncology · 2021Review
- miR-486 is involved in the pathogenesis of acute myeloid leukemia by regulating JAK-STAT signaling.Naunyn-Schmiedeberg's archives of pharmacology · 2021Article
- SPTBN1 inhibits inflammatory responses and hepatocarcinogenesis via the stabilization of SOCS1 and downregulation of p65 in hepatocellular carcinoma.Theranostics · 2021Article
- Resveratrol suppresses the growth and metastatic potential of cervical cancer by inhibiting STAT3Cancer medicine · 2020Article
51 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 4 institutions in 1 country.
Funding
Abstract
Hepatocellular carcinoma (HCC) is the third leading cause of cancer deaths worldwide, with few effective therapeutic options for advanced disease. At least 40% of HCCs are clonal, potentially arising from STAT3+, NANOG+ and OCT3/4+ liver progenitor/stem cell transformation, along with inactivation of transforming growth factor-beta (TGF-beta) signaling. Here we report significantly greater signal transducer and activator of transcription 3 (STAT3) and tyrosine phosphorylated STAT3 in human HCC tissues (P<0.0030 and P<0.0455, respectively) than in human normal liver. Further, in HCC cells with loss of response to TGF-beta, NSC 74859, a STAT3-specific inhibitor, markedly suppresses growth. In contrast, CD133(+) status did not affect the response to STAT3 inhibition: both CD133(+) Huh-7 cells and CD133(-) Huh-7 cells are equally sensitive to NSC 74859 treatment and STAT3 inhibition, with an IC(50) of 100 muM. Thus, the TGF-beta/beta2 spectrin (beta2SP) pathway may reflect a more functional 'stem/progenitor' state than CD133. Furthermore, NSC 74859 treatment of Huh-7 xenografts in nude mice significantly retarded tumor growth, with an effective dose of only 5 mg/kg. Moreover, NSC 74859 inhibited tyrosine phosphorylation of STAT3 in HCC cells in vivo. We conclude that inhibiting interleukin 6 (IL6)/STAT3 in HCCs with inactivation of the TGF-beta/beta2SP pathway is an effective approach in management of HCCs. Thus, IL6/STAT3, a major signaling pathway in HCC stem cell renewal and proliferation, can provide a novel approach to the treatment of specific HCCs.
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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.