ArticleMolecular carcinogenesis2017
Downregulation of STAT3/NF-κB potentiates gemcitabine activity in pancreatic cancer cells.
Article in Molecular carcinogenesis, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.
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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
25 citing papers in PubMed, 1 synthesis or guideline pooled it, 40 citations in OpenAlex.
- Herbals and Plants in the Treatment of Pancreatic Cancer: A Systematic Review of Experimental and Clinical Studies.Nutrients · 2022Pooled it
- TRPV6-Mediated CaCancers · 2026Review
- FASN contributes to ADM resistance of diffuse large B-cell lymphoma by inhibiting ferroptosis via nf-κB/STAT3/GPX4 axis.Cancer biology & therapy · 2024Article
- Exploring the role of antigen-presenting cancer-associated fibroblasts and CD74 on the pancreatic ductal adenocarcinoma tumor microenvironment.Medical oncology (Northwood, London, England) · 2024Review
- Tumor-derived exosome PPP3CB induce gemcitabine resistance by regulating miR-298/STAT3 in pancreatic cancer.Heliyon · 2024Article
- BP1003 Decreases STAT3 Expression and Its Pro-Tumorigenic Functions in Solid Tumors and the Tumor Microenvironment.Biomedicines · 2024Article
- Cancer Immunotherapy Using Bioengineered Micro/Nano Structured Hydrogels.Advanced healthcare materials · 2023Review
- A first-in-class pan-lysyl oxidase inhibitor impairs stromal remodeling and enhances gemcitabine response and survival in pancreatic cancer.Nature cancer · 2023Article
- Overcoming Acquired Drug Resistance to Cancer Therapies through Targeted STAT3 Inhibition.International journal of molecular sciences · 2023Review
- Genome-Wide CRISPR Screening Identifies DCK and CCNL1 as Genes That Contribute to Gemcitabine Resistance in Pancreatic Cancer.Cancers · 2022Article
- The natural product berberine synergizes with osimertinib preferentially against MET-amplified osimertinib-resistant lung cancer via direct MET inhibition.Pharmacological research · 2022Article
- Network pharmacology and molecular docking to elucidate the mechanism of pulsatilla decoction in the treatment of colon cancer.Frontiers in pharmacology · 2022Article
- NF-κB and Pancreatic Cancer; Chapter and Verse.Cancers · 2021Review
- Noncoding RNAs Associated with Therapeutic Resistance in Pancreatic Cancer.Biomedicines · 2021Review
- GATA4 Regulates Inflammation-Driven Pancreatic Ductal Adenocarcinoma Progression.Frontiers in cell and developmental biology · 2021Article
- Review
- Phospho-valproic acid (MDC-1112) reduces pancreatic cancer growth in patient-derived tumor xenografts and KPC mice: enhanced efficacy when combined with gemcitabine.Carcinogenesis · 2020Article
- Deoxyelephantopin induces apoptosis via oxidative stress and enhances gemcitabine sensitivityAging · 2020Article
- Nintedanib inhibits intrahepatic cholangiocarcinoma aggressiveness via suppression of cytokines extracted from activated cancer-associated fibroblasts.British journal of cancer · 2020Article
- Synthesis and Anticancer Activity of Novel 9-International journal of molecular sciences · 2019Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
Abstract
There is an unmet need to develop new agents or strategies against therapy resistant pancreatic cancer (PanCA). Recent studies from our laboratory showed that STAT3 negatively regulates NF-κB and that inhibition of this crosstalk using Nexrutine® (Nx) reduces transcriptional activity of COX-2. Inhibition of these molecular interactions impedes pancreatic cancer cell growth as well as reduces fibrosis in a preclinical animal model. Nx is an extract derived from the bark of Phellodendron amurense and has been utilized in traditional Chinese medicine as antidiarrheal, astringent, and anti-inflammatory agent for centuries. We hypothesized that "Nx-mediated inhibition of survival molecules like STAT3 and NF-κB in pancreatic cancer cells will improve the efficacy of the conventional chemotherapeutic agent, gemcitabine (GEM)." Therefore, we explored the utility of Nx, one of its active constituents berberine and its derivatives, to enhance the effects of GEM. Using multiple human pancreatic cancer cells we found that combination treatment with Nx and GEM resulted in significant alterations of proteins in the STAT3/NF-κB signaling axis culminating in growth inhibition in a synergistic manner. Furthermore, GEM resistant cells were more sensitive to Nx treatment than their parental GEM-sensitive cells. Interestingly, although berberine, the Nx active component used, and its derivatives were biologically active in GEM sensitive cells they did not potentiate GEM activity when used in combination. Taken together, these results suggest that the natural extract, Nx, but not its active component, berberine, has the potential to improve GEM sensitivity, perhaps by down regulating STAT3/NF-κB signaling. © 2016 Wiley Periodicals, Inc.
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