ArticleJournal of experimental & clinical cancer research : CR2019
Rhein sensitizes human pancreatic cancer cells to EGFR inhibitors by inhibiting STAT3 pathway.
Article in Journal of experimental & clinical cancer research : CR, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 94 citations in OpenAlex.
- Rhein and its derivatives: potential anti-tumor drugs and corresponding targeted mechanism.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2026Review
- Network Pharmacology, Molecular Docking, andCurrent topics in medicinal chemistry · 2026Article
- Synergistic Interactions of Anthraquinones with Conventional Cancer Therapies.Combinatorial chemistry & high throughput screening · 2026Review
- Surface plasmon resonance microscopy reveals N-glycosylation driven modulation of affinity and avidity of ErbB receptors in whole single pancreatic cancer cells.Glycobiology · 2025Article
- From Nature to Nanomedicine: Enhancing the Antitumor Efficacy of Rhein, Curcumin, and Resveratrol.Medicina (Kaunas, Lithuania) · 2025Review
- Peptide hydrogel-drug conjugates for tailored disease treatment.Materials today. Bio · 2025Review
- Fluorescent Rhein-Loaded Liposomes for In Vivo Biodistribution Study.Pharmaceutics · 2025Article
- Palindrome-mediated DNA nanotubes with cell-specific aptamers to improve targeted antitumor effects and reduce toxicity on non-small cell lung cancer.Science China. Life sciences · 2025Article
- Bibliometric analysis of rhein in the treatment of tumors.Frontiers in oncology · 2025Article
- Development of Traditional Chinese Medicine in combination with EGFR Inhibitors against Cancer.Journal of Cancer · 2025Review
- The Activity of 1,8-Dihydroanthraquinone Derivatives in Nervous System Cancers.Molecules (Basel, Switzerland) · 2024Review
- Rhein suppresses esophageal cancer development by regulating cell cycle through DNMT3B gene.Medical oncology (Northwood, London, England) · 2024Article
- Design, synthesis and biological evaluation of rhein-piperazine-furanone hybrids as potential anticancer agents.RSC medicinal chemistry · 2024Article
- Natural products as inhibitors against pancreatic cancer cell proliferation and invasion: possible mechanisms.American journal of cancer research · 2024Review
- Pancreatic Stellate Cells and the Targeted Therapeutic Strategies in Chronic Pancreatitis.Molecules (Basel, Switzerland) · 2023Review
- The In Vitro Anti-Parasitic Activities of Emodin towardPharmaceuticals (Basel, Switzerland) · 2023Article
- STAT3 promotes RNA polymerase III-directed transcription by controlling the miR-106a-5p/TP73 axis.eLife · 2023Article
- Review
- Research advances of N6-methyladenosine in diagnosis and therapy of pancreatic cancer.Journal of clinical laboratory analysis · 2022Review
- Inhibition of STAT3Cell death discovery · 2022Article
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundRhein is a lipophilic anthraquinone extensively found in medicinal herbs. Emerging evidence suggests that rhein has significant antitumor effects, supporting its potential use as an antitumor agent. The IL6/STAT3 signaling pathway has been suggested as an attractive target for the discovery of novel cancer therapeutics.
methodsThe human pancreatic cancer cell lines AsPC-1, Patu8988T, BxPC-3 and PANC-1, and immunodeficient mice were chosen as models to study the effects of rhein. The potent antiproliferative and proapoptotic effects of rhein were examined by cell viability, cellular morphology, apoptosis and colony formation assays. The STAT3 luciferase report assay, immunostaining analysis and Western blot analysis revealed the inhibition of the IL6/STAT3 signaling axis.
resultsApoptosis was induced by adjunctive use of rhein with epidermal growth factor receptor (EGFR) inhibitors in pancreatic cancer cells as verified by cell apoptosis analysis and changes in the expression level of apoptotic/anti-apoptotic proteins BCL-2, BAX, Caspase 3 and Cl-PARP. Suppression of the phosphorylation of STAT3 and EGFR were also observed as a result of the treatment with a combination of rhein and EGFR inhibitors. Most interestingly, it was found that rhein considerably sensitized cells to erlotinib, thus suppressing tumor growth in PANC-1 and BxPC-3 xenograft models. The in vivo anti-tumor effect was associated with increased apoptosis and combined inhibition of the STAT3 and EGFR pathways in tumor remnants.
conclusionsRhein sensitizes human pancreatic cancer cells to EGFR inhibitors through inhibition of STAT3. Taken together, the results indicate that rhein offers a novel blueprint for pancreatic cancer therapy, particularly when combined with EGFR inhibitors.
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