{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T15:41:40Z","timestamp":1776958900160,"version":"3.51.4"},"reference-count":80,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2021,4,22]],"date-time":"2021-04-22T00:00:00Z","timestamp":1619049600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100018712","name":"Universitatea de Medicin\u0103 \u015fi Farmacie Iuliu Ha\u0163ieganu Cluj-Napoca","doi-asserted-by":"publisher","award":["Grant No. 1680\/84\/19.01.2018"],"award-info":[{"award-number":["Grant No. 1680\/84\/19.01.2018"]}],"id":[{"id":"10.13039\/501100018712","id-type":"DOI","asserted-by":"publisher"}]},{"name":"European Social Found, Human Capital Operational Programme 2014-2020","award":["Grant No. POCU\/380\/6\/13\/125171"],"award-info":[{"award-number":["Grant No. POCU\/380\/6\/13\/125171"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Background: Melanoma patients stop responding to targeted therapies mainly due to mitogen activated protein kinase (MAPK) pathway re-activation, phosphoinositide 3 kinase\/the mechanistic target of rapamycin (PI3K\/mTOR) pathway activation or stromal cell influence. The future of melanoma treatment lies in combinational approaches. To address this, our in vitro study evaluated if lower concentrations of Celecoxib (IC50 in nM range) could still preserve the chemopreventive effect on melanoma cells treated with trametinib. Materials and Methods: All experiments were conducted on SK-MEL-28 human melanoma cells and BJ human fibroblasts, used as co-culture. Co-culture cells were subjected to a celecoxib and trametinib drug combination for 72 h. We focused on the evaluation of cell death mechanisms, melanogenesis, angiogenesis, inflammation and resistance pathways. Results: Low-dose celecoxib significantly enhanced the melanoma response to trametinib. The therapeutic combination reduced nuclear transcription factor (NF)\u2013kB (p &lt; 0.0001) and caspase-8\/caspase-3 activation (p &lt; 0.0001), inhibited microphthalmia transcription factor (MITF) and tyrosinase (p &lt; 0.05) expression and strongly down-regulated the phosphatidylinositol-3-kinase\/protein kinase B (PI3K\/AKT) signaling pathway more significantly than the control or trametinib group (p &lt; 0.0001). Conclusion: Low concentrations of celecoxib (IC50 in nM range) sufficed to exert antineoplastic capabilities and enhanced the therapeutic response of metastatic melanoma treated with trametinib.<\/jats:p>","DOI":"10.3390\/ijms22094387","type":"journal-article","created":{"date-parts":[[2021,4,22]],"date-time":"2021-04-22T13:59:14Z","timestamp":1619099954000},"page":"4387","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Celecoxib as a Valuable Adjuvant in Cutaneous Melanoma Treated with Trametinib"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5997-8586","authenticated-orcid":false,"given":"Diana Valentina","family":"Tudor","sequence":"first","affiliation":[{"name":"Department of Physiology, Faculty of Medicine, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ioana","family":"B\u00e2ldea","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3034-3659","authenticated-orcid":false,"given":"Diana Elena","family":"Olteanu","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0898-0547","authenticated-orcid":false,"given":"Eva","family":"Fischer-Fodor","sequence":"additional","affiliation":[{"name":"\u201cProf. Dr. Ion Chiricu\u021b\u0103\u201d Oncology Institute, 400015 Cluj-Napoca, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Virag","family":"Piroska","sequence":"additional","affiliation":[{"name":"\u201cProf. Dr. Ion Chiricu\u021b\u0103\u201d Oncology Institute, 400015 Cluj-Napoca, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0687-7180","authenticated-orcid":false,"given":"Mihai","family":"Lupu","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tudor","family":"C\u0103linici","sequence":"additional","affiliation":[{"name":"Department of Medical Informatics and Biostatistics, Faculty of Medicine, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, 400349 Cluj-Napoca, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roxana Maria","family":"Decea","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7447-4925","authenticated-orcid":false,"given":"Gabriela Adriana","family":"Filip","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,4,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Roesch, A., and Melanoma, B.C. 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