ArticlePloS one2021
Treatment of 13-cis retinoic acid and 1,25-dihydroxyvitamin D3 inhibits TNF-alpha-mediated expression of MMP-9 protein and cell invasion through the suppression of JNK pathway and microRNA 221 in human pancreatic adenocarcinoma cancer cells.
Article in PloS one, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
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Who cites it
14 citing papers in PubMed, 1 synthesis or guideline pooled it, 17 citations in OpenAlex.
- Vitamin D and Pancreatic Ductal Adenocarcinoma-A Review of a Complicated Relationship.Nutrients · 2024Pooled it
- Systems pharmacology, structural modeling, and experimental validation reveal retinoic acid as a modulator of immune-fibrotic networks in chronic kidney disease.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Review
- Review
- Vitamin A and its influence on tumour extracellular matrix.Discover oncology · 2025Review
- Targeting stromal components in pancreatic ductal adenocarcinoma: a review.Ecancermedicalscience · 2025Review
- Pet Wellness and Vitamin A: A Narrative Overview.Animals : an open access journal from MDPI · 2024Review
- Vitamin A, D, E, and K as Matrix Metalloproteinase-2/9 Regulators That Affect Expression and Enzymatic Activity.International journal of molecular sciences · 2023Review
- Role of Vitamin D in Head and Neck Cancer-Immune Function, Anti-Tumour Effect, and Its Impact on Patient Prognosis.Nutrients · 2023Review
- Matrix Metalloproteinases and Glaucoma.Biomolecules · 2022Review
- Review
- miR-221/222 as biomarkers and targets for therapeutic intervention on cancer and other diseases: A systematic review.Molecular therapy. Nucleic acids · 2022Review
- Pancreatic Ductal Adenocarcinoma: New Insights into the Actions of Vitamin A.Oncology research and treatment · 2022Review
- Downregulation of Methionine Cycle GenesInternational journal of molecular sciences · 2022Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Human pancreatic ductal adenocarcinoma (PDAC) is a deadly cancer type with a very high mortality rate. Inflammatory cytokine such as tumor necrosis factor- alpha (TNF-α) plays a pivotal role in the progression of PDAC. Recently, suppression of cell invasion by preventive agents has received considerable attention in the prevention of metastatic tumors. Several clinical studies suggested that natural forms or analogues of fat-soluble vitamins such as vitamin A and vitamin D can work as anti-cancer agents to inhibit the development of cancer. In this study, our results demonstrated that co-treatment of 13-cis retinoic acid (13-cis RA) and 1,25-dihydroxyvitamin D3 (1,25-VD3) significantly inhibited TNF-α mediated cell invasion in PDAC in vitro. Cotreatment of 13-cis RA and 1,25-VD3 also inhibited TNF-α mediated expression of matrix metalloproteinase-9 (MMP-9) protein through blocking c-Jun N-terminal kinase (JNK) and nuclear factor kappa B (NF-κB) signaling pathways. Our results demonstrated that treatment of TNF-α lead to a decreased expression of tissue inhibitor of metalloproteinase- 3 (TIMP-3) protein and an induction of MMP-9 protein and cell invasion through an upregulation of microRNA-221 (miR-221) in human PDAC cells. Moreover, treatment of SP600125 (a specific inhibitor of JNK pathway) or cotreatment of 13-cis RA and 1,25-VD3 significantly induced a decreased expression of miR-221 and an increased expression of TIMP-3 protein. These results suggest that 13-cis RA and 1,25-VD3 significantly suppress TNF-α mediated cell invasion and therefore potentially act as preventive agents against PDAC.
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Registered trials
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