{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T13:17:22Z","timestamp":1770815842777,"version":"3.50.1"},"reference-count":104,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,6,4]],"date-time":"2025-06-04T00:00:00Z","timestamp":1748995200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Chemoresistance and disease relapses in epithelial ovarian cancer (EOC) highlight the need for novel therapeutic strategies. Here, we investigated phosphodiesterase 7A (PDE7A) as a potential target in ovarian cancer treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Gene expression was performed by RNA sequencing data comparing high-grade serous ovarian carcinoma (HGSOC) and fallopian tube samples. The PDE7 inhibitor BRL 50481, alone or combined with paclitaxel (PTX), was tested in drug-sensitive A2780 and multi-resistant OVCAR3 cells by Diphenyltetrazolium bromide (MTT) assay. To validate data from the high throughput RNA-sequencing assays, RT-qPCR and Immunoblotting were performed. Cytokine expression was analyzed by RT-qPCR and the quantification was obtained by ELISA. Scanning and Transmission Electron Microscopy were also carried out.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results and discussion<\/jats:title><jats:p>MTT assays revealed that while BRL 50481 reduced metabolic cellular viability (MCV) in A2780 (IC50 = 200 \u03bcM), its combination with PTX decreased MCV in both lines, reducing PTX IC50 by 103- and 625-fold in A2780 and OVCAR3, respectively. PDE7 inhibition suppressed the PI3K\/AKT\/mTOR pathway, upregulated the pro-apoptotic protein Bcl-2 Associated X-protein (BAX) in A2780, and increased IL-6 expression in OVCAR3. Pretreatment with BRL 50481 followed by PTX downregulated vimentin and octamer-binding transcription factor (OCT4), while inducing morphological changes and mitochondrial cristae alterations. Inhibiting PDE7 can enhance the paclitaxel-induced apoptosis by promoting mitochondrial dysfunction and suppressing survival pathways, thereby improving ovarian cancer treatment efficacy. The results need to be validated in additional in vivo models.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fphar.2025.1566330","type":"journal-article","created":{"date-parts":[[2025,6,4]],"date-time":"2025-06-04T05:37:54Z","timestamp":1749015474000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Phosphodiesterase 7: a potential novel therapeutic target in ovarian cancer"],"prefix":"10.3389","volume":"16","author":[{"given":"Nayara Gusm\u00e3o","family":"Tessarollo","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isabella dos Santos","family":"Guimar\u00e3es","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diandra Zipinotti","family":"dos Santos","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Taciane Barbosa","family":"Henriques","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paulo Cilas Morais","family":"Lyra-Junior","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Josiany","family":"Carlos de Souza","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tatiana Massariol","family":"Pimenta","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B\u00e1rbara da Silva","family":"Martins","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Solenny Maria Silva","family":"Butzene","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos\u00e9 Matheus Sim\u00f5es","family":"Padilha","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leide Laura Figueiredo","family":"Maciel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jo\u00e3o Carlos de Aquino","family":"Almeida","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ian Victor","family":"Silva","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leticia Batista Azevedo","family":"Rangel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,6,4]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"e25","DOI":"10.1111\/odi.12275","article-title":"Cyclic nucleotide phosphodiesterases: important signaling modulators and therapeutic targets","volume":"21","author":"Ahmad","year":"2015","journal-title":"Oral Dis."},{"key":"B2","doi-asserted-by":"publisher","first-page":"6246","DOI":"10.3390\/cancers14246246","article-title":"Mechanisms of drug resistance in ovarian cancer and associated gene targets","volume":"14","author":"Alatise","year":"2022","journal-title":"Cancers (Basel)"},{"key":"B3","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1016\/bs.podrm.2018.11.001","article-title":"Paclitaxel","volume":"44","author":"Alqahtani","year":"2019","journal-title":"Relat. 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