ArticleCancer prevention research (Philadelphia, Pa.)2017
Sildenafil Suppresses Inflammation-Driven Colorectal Cancer in Mice.
Article in Cancer prevention research (Philadelphia, Pa.), 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers, 2 of them syntheses that pooled it.
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Who cites it
47 citing papers in PubMed, 2 syntheses or guidelines pooled it, 80 citations in OpenAlex.
- Long-term effects of phosphodiesterase-5 inhibitors on cardiovascular outcomes and death: a systematic review and meta-analysis.European heart journal. Cardiovascular pharmacotherapy · 2024Pooled it
- Phosphodiesterase type 5 inhibitors use and risk of colorectal cancer: a systematic review and meta-analysis.International journal of colorectal disease · 2021Pooled it
- Effect of a three-piece inflatable penile prosthesis combined with a phosphodiesterase-5 inhibitor on erectile dysfunction.The Journal of international medical research · 2021Trial
- Assessing the impact of phosphodiesterase 5 inhibitors on survival in men after treatment for rectal cancer.Frontiers in oncology · 2026Article
- Inhibition of AhR improves cortical bone and skeletal muscle function via preservation of neuromuscular junctions.JCI insight · 2025Article
- Genetically proxied inhibition of Phosphodiesterase-5 and cancer risks: A drug-target Mendelian randomization analysis.Scientific reports · 2025Article
- Cyclic nucleotide phosphodiesterases as drug targets.Pharmacological reviews · 2025Review
- Rational Design and Optimization of Novel PDE5 Inhibitors for Targeted Colorectal Cancer Therapy: An In Silico Approach.International journal of molecular sciences · 2025Article
- Repurposing of phosphodiesterase-5 inhibitor sildenafil as a therapeutic agent to prevent gastric cancer growth through suppressing c-MYC stability for IL-6 transcription.Communications biology · 2025Article
- Susceptibility of different mice species to chemical induction of colorectal cancer by 1,2-dimethylhydrazine.Journal of the Egyptian National Cancer Institute · 2025Article
- Novel Celecoxib Derivative, RF26, Blocks Colon Cancer Cell Growth by Inhibiting PDE5, Activating cGMP/PKG Signaling, and Suppressing β-catenin-dependent Transcription.Anti-cancer agents in medicinal chemistry · 2025Article
- Rethinking of phosphodiesterase 5 inhibition: the old, the new and the perspective in human health.Frontiers in endocrinology · 2024Review
- Exploring the Multifaceted Potential of Sildenafil in Medicine.Medicina (Kaunas, Lithuania) · 2023Review
- A Non-Systemic Phosphodiesterase-5 Inhibitor Suppresses Colon Proliferation in Mice.International journal of molecular sciences · 2023Article
- Sildenafil Inhibits the Growth and Epithelial-to-mesenchymal Transition of Cervical Cancer via the TGF-β1/Smad2/3 Pathway.Current cancer drug targets · 2023Article
- Uncoupled nitric oxide synthase activity promotes colorectal cancer progression.Frontiers in oncology · 2023Article
- Type-2 cGMP-dependent protein kinase suppresses proliferation and carcinogenesis in the colon epithelium.Carcinogenesis · 2022Article
- Inhibition of Colon Cancer Cell Growth by Phosphodiesterase Inhibitors Is Independent of cGMP Signaling.The Journal of pharmacology and experimental therapeutics · 2022Article
- Pulmonary artery targeted therapy in treatment of COVID-19 related ARDS. Literature review.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2022Review
- A β-Catenin-TCF-Sensitive Locus Control Region Mediates GUCY2C Ligand Loss in Colorectal Cancer.Cellular and molecular gastroenterology and hepatology · 2022Article
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
Intestinal cyclic guanosine monophosphate (cGMP) signaling regulates epithelial homeostasis and has been implicated in the suppression of colitis and colon cancer. In this study, we investigated the cGMP-elevating ability of the phosphodiesterase-5 (PDE5) inhibitor sildenafil to prevent disease in the azoxymethane/dextran sulfate sodium (AOM/DSS) inflammation-driven colorectal cancer model. Treatment of mice with sildenafil activated cGMP signaling in the colon mucosa and protected against dextran-sulfate sodium (DSS)-induced barrier dysfunction. In mice treated with AOM/DSS, oral administration of sildenafil throughout the disease course reduced polyp multiplicity by 50% compared with untreated controls. Polyps that did form in sildenafil treated mice were less proliferative and more differentiated compared with polyps from untreated mice, but apoptosis was unaffected. Polyps in sildenafil treated mice were also less inflamed; they exhibited reduced myeloid-cell infiltration and reduced expression of iNOS, IFNγ, and IL6 compared with untreated controls. Most of the protection conferred by sildenafil was during the initiation stage of carcinogenesis (38% reduction in multiplicity). Administration of sildenafil during the later promotion stages did not affect multiplicity but had a similar effect on the polyp phenotype, including increased mucus production, and reduced proliferation and inflammation. In summary, the results demonstrate that oral administration of sildenafil suppresses polyp formation and inflammation in mice treated with AOM/DSS. This validation of PDE5 as a target highlights the potential therapeutic value of PDE5 inhibitors for the prevention of colitis-driven colon cancer in humans.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.