{"doi":"10.1038/s42003-025-07519-9","title":"Repurposing of phosphodiesterase-5 inhibitor sildenafil as a therapeutic agent to prevent gastric cancer growth through suppressing c-MYC stability for IL-6 transcription","abstract":null,"journal":"Communications Biology","year":2025,"id":641967,"datarank":0.42498200160843247,"base_score":2.833213344056216,"endowment":2.833213344056216,"self_citation_contribution":0.42498200160843247,"citation_network_contribution":0.0,"self_endowment_contribution":0.42498200160843247,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":16,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1669436,"name":"Wuqing Huang","orcid":null,"position":1,"is_corresponding":false},{"id":1406211,"name":"Donghua Huang","orcid":"0000-0001-9988-3146","position":2,"is_corresponding":false},{"id":401245,"name":"Zhou Xu","orcid":null,"position":3,"is_corresponding":false},{"id":1669437,"name":"Qingfeng Xie","orcid":null,"position":4,"is_corresponding":false},{"id":1434578,"name":"Xin Tan","orcid":"0009-0005-4401-6690","position":5,"is_corresponding":false},{"id":781759,"name":"Wenjun He","orcid":"0000-0003-2043-1329","position":6,"is_corresponding":false},{"id":1669438,"name":"Weihao Yang","orcid":null,"position":7,"is_corresponding":false},{"id":89756,"name":"Guoxin Li","orcid":"0000-0003-2773-7048","position":8,"is_corresponding":false},{"id":34248,"name":"Jianguang Ji","orcid":"0000-0003-0324-9496","position":9,"is_corresponding":false},{"id":949429,"name":"Hao Liu","orcid":"0000-0003-1227-2954","position":10,"is_corresponding":false},{"id":1669435,"name":"Zhenzhan Zhang","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Repurposing of phosphodiesterase-5 inhibitor sildenafil as a therapeutic agent to prevent gastric cancer growth through suppressing c-MYC stability for IL-6 transcription","abstract":"Phosphodiesterase-5 (PDE5) inhibitors have shown promise as anti-cancer agents in malignancies. However, their specific effects on gastric cancer (GC) and the underlying mechanisms remain elusive. Our aim was to investigate this by combining evidence from population-based studies with data obtained from in vivo and in vitro experiments. By combing a couple of nationwide Swedish registers, GC patients who received PDE5 inhibitors were compared to matched controls while adjusting for confounding factors. The anti-tumor effect and mechanism of the PDE5 inhibitor sildenafil were evaluated via using tumor cells, patient-derived tumor organoids and xenograft animal models in GC. A total of 161 Swedish GC patients from a nationwide population-based cohort who received post-diagnostic PDE5 inhibitors demonstrated lower cancer-specific mortality compared to the controls (HR = 0.66, 95% CI = 0.47-0.92, P = 0.016). Functionally, the PDE5 inhibitor sildenafil exhibited the suppressive ability to prevent oncogenic growth in GC. Mechanistically, sildenafil restrained GC growth by directly activating PKG through PDE5 inhibition for regulating c-MYC expression via its phosphorylation and ubiquitination degradation, thereby suppressing c-MYC stability for IL-6 transcription within the downstream IL-6/JAK/STAT3 signalling pathway. The PDE5 inhibitor sildenafil may serve as a promising adjuvant for GC therapy if further randomized clinical trials confirm its efficacy.","is_dataset_classified":null,"base_score":2.833213344056216,"endowment":2.833213344056216,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"39827331","pmcid":"PMC11742916","openalex_id":"https://openalex.org/W4406555870","authors":[],"funders":[{"funder_name":"the Key Areas Research and Development Programs of Guangdong Province","grant_id":"","title":null},{"funder_name":"the Natural Science Foundation of Guangdong Province","grant_id":"","title":null},{"funder_name":"the National Natural Science Foundation of China","grant_id":"","title":null},{"funder_name":"the President Foundation of Nanfang Hospital, Southern Medical University","grant_id":"","title":null}],"total_grants":4,"fwci":6.4074,"citation_percentile":0.97219275,"influential_citations":0,"citation_trend":[{"year":2025,"count":11},{"year":2026,"count":5}],"oa_status":"gold","license":"cc-by-nc-nd","oa_locations":[{"url":"https://www.nature.com/articles/s42003-025-07519-9.pdf","host_type":"journal"},{"url":"https://doi.org/10.1038/s42003-025-07519-9","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/39827331","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/11742916","host_type":"repository"},{"url":"https://doaj.org/article/c6f24823ec5d42b49b64edc4f7af5368","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC11742916","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC11742916?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":["Phosphodiesterase function and regulation","Mast cells and histamine","Histone Deacetylase Inhibitors Research"],"mesh_terms":["Sildenafil Citrate","Aged","Animals","Female","Humans","Male","Mice, Nude","Middle Aged","Stomach Neoplasms","Transcription, Genetic","Interleukin-6","Gene Expression Regulation, Neoplastic","Proto-Oncogene Proteins c-myc","Xenograft Model Antitumor Assays","Cell Line, Tumor","Cell Proliferation","Mice","Cyclic Nucleotide Phosphodiesterases, Type 5","Drug Repositioning","Phosphodiesterase 5 Inhibitors"],"keywords":["Sildenafil","cGMP-specific phosphodiesterase type 5","Medicine","Pharmacology","Population","Cancer","Cancer research","Internal medicine"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-07T21:04:33.525646Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}