ArticleJournal of experimental & clinical cancer research : CR2017
Gambogic acid sensitizes gemcitabine efficacy in pancreatic cancer by reducing the expression of ribonucleotide reductase subunit-M2 (RRM2).
Article in Journal of experimental & clinical cancer research : CR, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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Who cites it
58 citing papers in PubMed.
- Synergistic anti-tumor activity of andrographolide and gemcitabine in intrahepatic cholangiocarcinoma through inhibition of RRM2 and the JAK/STAT3 pathway.Cancer chemotherapy and pharmacology · 2026Article
- Crude Venom from Sea AnemoneMarine drugs · 2026Article
- Development of a ratiometric fluorescence nanosensor for evaluating precision chemotherapy of osteosarcoma through real-time monitoring of caspase-3 activity.Mikrochimica acta · 2025Article
- Targeting RRM2 with dual-modal theranostic smart nanoresponder overcomes osimertinib resistance and triggers immune remodeling in NSCLC.Science advances · 2025Article
- DEAD/H-box RNA helicase 10 promotes pancreatic cancer cell proliferationWorld journal of gastrointestinal oncology · 2025Article
- Gambogenic Acid Suppresses Malignant Progression of Non-Small Cell Lung Cancer via GCH1-Mediated Ferroptosis.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Investigation of bioavailability and anti-pancreatic cancer efficacy of a self-nanoemulsifying erlotinib delivery system.Therapeutic delivery · 2025Article
- Bioinformatics Analysis Screening and Identification of Key Biomarkers and Drug Targets in Human Glioblastoma.Current medicinal chemistry · 2025Article
- Antitumor effects and mechanisms of traditional Chinese medicine gamboge: A review.Frontiers in pharmacology · 2025Review
- Unveiling the resistance to therapies in pancreatic ductal adenocarcinoma.Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy · 2024Review
- The potential of ribonucleotide reductase M2 as a novel prognostic maker and therapeutic target to inhibit medulloblastoma proliferation, migration, and invasiveness.Pediatric discovery · 2024Article
- AI-powered omics-based drug pair discovery for pyroptosis therapy targeting triple-negative breast cancer.Nature communications · 2024Article
- Emerging mechanisms and promising approaches in pancreatic cancer metabolism.Cell death & disease · 2024Review
- Transcription factor FOXF2 promotes the development and progression of pancreatic cancer by targeting MSI2.Oncology reports · 2024Article
- Proteomics Identifies LUC7L3 as a Prognostic Biomarker for Hepatocellular Carcinoma.Current issues in molecular biology · 2024Article
- Role of Phytoconstituents in Cancer Treatment: A Review.Recent advances in food, nutrition & agriculture · 2024Review
- Design, Synthesis and Anti-cancer Evaluation of Nitrogen-containing Derivatives of 30-Carboxyl of Gambogic Acid.Anti-cancer agents in medicinal chemistry · 2024Article
- E2F1 rs3213150 polymorphism influences cytarabine sensitivity and prognosis in patients with acute myeloid leukemia.Annals of hematology · 2023Article
- Knockdown of TACC3 inhibits tumor cell proliferation and increases chemosensitivity in pancreatic cancer.Cell death & disease · 2023Article
- PAK4 inhibition significantly potentiates Gemcitabine activity in PDAC cells via inhibition of Wnt/β-catenin, p-ERK/MAPK and p-AKT/PI3K pathways.Biochemistry and biophysics reports · 2023Article
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Authors and funding
6 authors.
Funding
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Abstract
backgroundPancreatic cancer is susceptible to gemcitabine resistance, and patients receive less benefit from gemcitabine chemotherapy. Previous studies report that gambogic acid possesses antineoplastic properties; however, to our knowledge, there have been no specific studies on its effects in pancreatic cancer. Therefore, the purpose of this study was to explore whether increases the sensitivity of pancreatic cancer to gemcitabine, and determine the synergistic effects of gambogic acid and gemcitabine against pancreatic cancer.
methodsThe effects of gambogic acid on cell viability, the cell cycle, and apoptosis were assessed using 4,5-dimethylthiazol-2-yl)-3,5-diphenylformazan (MTT) and flow cytometry in pancreatic cancer cell lines. Protein expression was detected by western blot analysis and mRNA expression was detected using q-PCR. A xenograft tumor model of pancreatic cancer was used to investigate the synergistic effects of gambogic acid and gemcitabine.
resultsGambogic acid effectively inhibited the growth of pancreatic cancer cell lines by inducing S-phase cell cycle arrest and apoptosis. Synergistic activity of gambogic acid combined with gemcitabine was observed in PANC-1 and BxPC-3 cells based on the results of MTT, colony formation, and apoptosis assays. Western blot results demonstrated that gambogic acid sensitized gemcitabine-induced apoptosis by enhancing the expression of cleaved caspase-3, cleaved caspase-9, cleaved-PARP, and Bax, and reducing the expression of Bcl-2. In particular, gambogic acid reduced the expression of the ribonucleotide reductase subunit-M2 (RRM2) protein and mRNA, a trend that correlated with resistance to gemcitabine through inhibition of the extracellular signal-regulated kinase (ERK)/E2F1 signaling pathway. Treatment with gambogic acid and gemcitabine significantly repressed tumor growth in the xenograft pancreatic cancer model. Immunohistochemistry results demonstrated a downregulation of p-ERK, E2F1, and RRM2 in mice receiving gambogic acid treatment and combination treatment.
conclusionsThese results demonstrate that gambogic acid sensitizes pancreatic cancer cells to gemcitabine in vitro and in vivo by inhibiting the activation of the ERK/E2F1/RRM2 signaling pathway. The results also indicate that gambogic acid treatment combined with gemcitabine might be a promising chemotherapy strategy for pancreatic cancer.
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