ArticleThe Journal of biological chemistry2010
Inhibition of STAT3 signaling blocks the anti-apoptotic activity of IL-6 in human liver cancer cells.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers, 1 of them a synthesis that pooled it.
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Who cites it
80 citing papers in PubMed, 1 synthesis or guideline pooled it, 158 citations in OpenAlex.
- Advances in the Prevention and Treatment of Obesity-Driven Effects in Breast Cancers.Frontiers in oncology · 2022Pooled it
- Calcitriol, the active form of vitamin D, induces cell death and purinergic signaling modulation in cutaneous melanoma cells.Medical oncology (Northwood, London, England) · 2026Article
- Targeting Inflammation and Immune Regulation in Chronic Inflammation Associated Cancers.Cancer science · 2026Review
- Postnatal hypoxic preconditioning attenuates lung damage from hyperoxia in newborn mice.Pediatric research · 2025Article
- The potential role of targeting the leptin receptor as a treatment for breast cancer in the context of hyperleptinemia: a literature review.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Interleukin-6 Modulation in Ovarian Cancer Necessitates a Targeted Strategy: From the Approved to Emerging Therapies.Cancers · 2024Review
- Sorcin Inhibits Mitochondrial Apoptosis by Interacting with STAT3 via NF-κB Pathway.International journal of molecular sciences · 2024Article
- Trastuzumab-induced human cardiomyocyte damage through the Notch2/JAK2/STAT3 pathway.Clinics (Sao Paulo, Brazil) · 2023Article
- Precision Anti-Cancer Medicines by Oligonucleotide Therapeutics in Clinical Research Targeting Undruggable Proteins and Non-Coding RNAs.Pharmaceutics · 2022Review
- JAK-STAT core cancer pathway: An integrative cancer interactome analysis.Journal of cellular and molecular medicine · 2022Review
- gp130/STAT3 signaling is required for homeostatic proliferation and anabolism in postnatal growth plate and articular chondrocytes.Communications biology · 2022Article
- Adenosine receptors differentially mediate enteric glial cell death induced byFrontiers in immunology · 2022Article
- Reposition of the anti-inflammatory drug diacerein in anSaudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2022Article
- Anti-carcinogenic effects of exercise-conditioned human serum: evidence, relevance and opportunities.European journal of applied physiology · 2021Review
- Revisiting IL-6 expression in the tumor microenvironment of classical Hodgkin lymphoma.Blood advances · 2021Article
- Potential Therapeutic Targets of Quercetin, a Plant Flavonol, and Its Role in the Therapy of Various Types of Cancer through the Modulation of Various Cell Signaling Pathways.Molecules (Basel, Switzerland) · 2021Review
- MicroRNA-140-5p regulates the proliferation, apoptosis and inflammation of RA FLSs by repressing STAT3.Experimental and therapeutic medicine · 2021Article
- Rugosic acid A, derived from Rosa rugosa Thunb., is novel inhibitory agent for NF-κB and IL-6/STAT3 axis in acute lung injury model.Phytotherapy research : PTR · 2020Article
- Cytokine regulation of apoptosis-induced apoptosis and apoptosis-induced cell proliferation in vascular smooth muscle cells.Apoptosis : an international journal on programmed cell death · 2020Article
- Transcription Factors in Cancer Development and Therapy.Cancers · 2020Review
20 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Interleukin-6 (IL-6) is a multifunctional cytokine, which may block apoptosis during inflammation to protect cells under very toxic conditions. However, IL-6 also activates STAT3 in many types of human cancer. Recent studies demonstrate that high levels of IL-6 are associated with hepatocellular carcinoma, the most common type of liver cancer. Here we reported that IL-6 promoted survival of human liver cancer cells through activating STAT3 in response to doxorubicin treatment. Endogenous IL-6 levels in SNU-449 cells were higher than in Hep3B cells. Meanwhile, SNU-449 cells were more resistant to doxorubicin than Hep3B cells. Addition of IL-6 induced STAT3 activation in Hep3B cells and led to protection against doxorubicin. In contrast, neutralizing IL-6 with anti-IL-6 antibody decreased survival of SNU-449 cells in response to doxorubicin. To elucidate the mechanism of the anti-apoptotic function of IL-6, we investigated if STAT3 mediated this drug resistance. Targeting STAT3 with STAT3 siRNA reduced the protection of IL-6 against doxorubicin-induced apoptosis, indicating that STAT3 signaling contributed to the anti-apoptotic effect of IL-6. Moreover, we further explored if a STAT3 small molecule inhibitor could abolish this anti-apoptotic effect. LLL12, a STAT3 small molecule inhibitor, blocked IL-6-induced STAT3 phosphorylation, resulting in attenuation of the anti-apoptotic activity of IL-6. Finally, neutralization of endogenous IL-6 with anti-IL-6 antibody or blockade of STAT3 with LLL12 lowered the recovery in SNU-449 cells after doxorubicin treatment. Therefore, our results demonstrated that targeting STAT3 signaling could interrupt the anti-apoptotic function of IL-6 in human liver cancer cells.
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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.