ArticleCancer medicine2024
The role of DPYD and the effects of DPYD suppressor luteolin combined with 5-FU in pancreatic cancer.
Article in Cancer medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed.
- Phytochemicals as Multitarget Therapeutics in Pancreatic Cancer: Mechanisms, Clinical Evidence, and Translational Challenges.Phytotherapy research : PTR · 2026Review
- Ellagic acid is associated with reduced pancreatic carcinogenesis and modulation of the IL-6/STAT3 pathway.Genes and environment : the official journal of the Japanese Environmental Mutagen Society · 2026Article
- Current situation and research progress of luteolin in the treatment of gastrointestinal malignant tumors.Discover oncology · 2026Review
- Leveraging the molecular insights and therapeutic potential of diet-derived-flavonoids against pancreatic ductal adenocarcinoma.Frontiers in pharmacology · 2026Review
- Unlocking the Potential of Bioactive Compounds in Pancreatic Cancer Therapy: A Promising Frontier.Biomolecules · 2025Review
- Exploring experimental models of prostate cancer in chemoprevention: Oxidative stress as a key pathway to translational research.Pathology international · 2025Review
- Roles of nucleotide metabolism in pancreatic cancer.Frontiers in immunology · 2025Review
- Potential anticancer effects and toxicity of flavones luteolin and apigeninJournal of environmental science and health. Part C, Toxicology and carcinogenesis · 2025Review
- The role of DPYD and the effects of DPYD suppressor luteolin combined with 5-FU in pancreatic cancer.Cancer medicine · 2024Article
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12 authors.
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Abstract
backgroundDespite advances in the treatment of cancer, pancreatic ductal adenocarcinoma (PDAC) remains highly lethal due to the lack of effective therapies. Our previous study showed that Luteolin (Lut), a flavonoid, suppressed pancreatocarcinogenesis and reduced the expression of dihydropyrimidine dehydrogenase (DPYD), an enzyme that degrades pyrimidines such as 5-fluorouracil (5-FU), in PDACs. In this study, we investigated the role of DPYD and evaluated the therapeutic potential of combining 5-FU with Lut in PDACs. METHODS AND
resultsPDAC cells overexpressing DPYD showed increased proliferation, and invasiveness, adding to the resistance to 5-FU. The xenograft tumors of DPYD-overexpressing PDAC cells also exhibit enhanced growth and invasion compared to the control xenograft tumors. RNA-seq analysis of the DPYD-overexpressing PDAC xenograft tumors revealed an upregulation of genes associated with metallopeptidase activity-MMP9 and MEP1A. Furthermore, the overexpression of MEP1A in PDAC was associated with invasion. Next, we investigated the combined effects of Lut, a DPYD suppressor, and 5-FU on DPYD-overexpressing xenograft tumors and PDAC of Pdx1-Cre; LSL-KrasG12D/+; Trp53flox/flox(KPPC) mice. Neither single administration of 5-FU nor Lut showed significant inhibitory effects; however, the combined administration of 5-FU and Lut exhibited a significant tumor-suppressive effect in both the xenograft tumors and KPPC models.
conclusionWe have elucidated that DPYD expression contributes to proliferation, invasiveness, and 5-FU resistance, in PDACs. The combination therapy of Lut and 5-FU holds the potential for enhanced efficacy against PDACs.
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