ArticleNaunyn-Schmiedeberg's archives of pharmacology2025
Melatonin augments anti-tumor activity and alleviates nephrotoxicity of gemcitabine in a pancreatic cancer xenograft model targeting P62/Keap1 pathway.
Article in Naunyn-Schmiedeberg's archives of pharmacology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed.
- Cardioprotective role of vincamine in cyclophosphamide-induced cardiotoxicity through modulation of AMPK/SIRT1, PI3K/Akt, and MAPK pathways.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Metabolomic, in vitro and preclinical evaluation of Auricularia polytricha mushroom.International microbiology : the official journal of the Spanish Society for Microbiology · 2026Article
- Modulation of the ACLY-AMPK axis by bempedoic acid suppresses NF-κB-driven inflammation, VEGF-Notch angiogenic crosstalk, and cell-cycle progression in Solid Ehrlich Carcinoma.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Fondaparinux attenuates methotrexate-induced hepatotoxicity by regulating coagulation, endothelial dysfunction, and inflammatory signaling via the TLR4/NLRP3 and NF-κB/IL-1β/MCP-1 pathways.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Buspirone attenuates cyclophosphamide-induced renal dysfunction in association with alterations in miR-205/EGLN2, Nrf2, and PERK/ATF4/CHOP signaling.Frontiers in pharmacology · 2026Article
- Melatonin as an anti-inflammatory hormone bridging migraine relief and cancer immunity enhancement: a literature review.Frontiers in immunology · 2025Review
- Melatonin: a natural guardian in cancer treatment.Frontiers in pharmacology · 2025Review
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Authors and funding
5 authors.
Funding
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Abstract
Although gemcitabine is a primary chemotherapy for pancreatic cancer, its effectiveness is limited by chemoresistance and nephrotoxicity, posing significant clinical challenges. Therefore, the development of novel therapeutic approaches to prevent pancreatic malignancy remains crucial. This study aimed to investigate the potential of melatonin in enhancing gemcitabine's anticancer efficacy while mitigating its nephrotoxic effects through modulation of the Keap1/p62 pathway. A pancreatic cancer xenograft model was established in rats, which received either gemcitabine (50 mg/kg, I.P.), melatonin (50 mg/kg, I.P.), or their combination three times per week for 2 weeks. Our findings demonstrate that melatonin potentiates gemcitabine's cancer-suppressing effects via modulation of the Kelch-like-ECH associated protein-1 (Keap1)/p62 pathway, resulting in reduced fibrosis, oxidative stress, and inflammatory markers. Additionally, melatonin significantly mitigated gemcitabine-induced nephrotoxicity. These results suggest that melatonin may serve as an adjuvant therapy in pancreatic cancer treatment, enhancing chemotherapy efficacy while reducing its adverse effects.
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