{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T13:25:53Z","timestamp":1770729953364,"version":"3.49.0"},"reference-count":66,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2024,10,22]],"date-time":"2024-10-22T00:00:00Z","timestamp":1729555200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fundo Europeu de Desenvolvimento Regional (FEDER)","award":["Portugal 2020"],"award-info":[{"award-number":["Portugal 2020"]}]},{"name":"Fundo Europeu de Desenvolvimento Regional (FEDER)","award":["IF\/00092\/2014\/CP1255\/CT0004"],"award-info":[{"award-number":["IF\/00092\/2014\/CP1255\/CT0004"]}]},{"name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia (FCT)","award":["Portugal 2020"],"award-info":[{"award-number":["Portugal 2020"]}]},{"name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia (FCT)","award":["IF\/00092\/2014\/CP1255\/CT0004"],"award-info":[{"award-number":["IF\/00092\/2014\/CP1255\/CT0004"]}]},{"name":"the Faculty of Medicine, University of Porto (FMUP)","award":["Portugal 2020"],"award-info":[{"award-number":["Portugal 2020"]}]},{"name":"the Faculty of Medicine, University of Porto (FMUP)","award":["IF\/00092\/2014\/CP1255\/CT0004"],"award-info":[{"award-number":["IF\/00092\/2014\/CP1255\/CT0004"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Applied Sciences"],"abstract":"<jats:p>The therapeutic potential of combining 5-FU with repurposed drugs such as Sildenafil, Tezosentan, Levosimendan, and Resveratrol was investigated in lung cancer treatment using the A549 cell line. This study aimed to enhance 5-FU efficacy while mitigating side effects and overcoming drug resistance. The cytotoxic effects of 5-FU were assessed via MTT assay, with an IC50 value of 5.03 \u00b5M for A549 cells. Subsequent experiments evaluated the impact of combining 5-FU with the aforementioned drugs on cell viability, clonogenic potential, and morphology. The results demonstrated that while Sildenafil and Tezosentan modestly improved 5-FU efficacy, Levosimendan reduced cell viability by 40% (p &lt; 0.01) and Resveratrol by over 50% (p &lt; 0.001), with clonogenicity reduced by up to 60% (p &lt; 0.001). These findings suggest that combining 5-FU with Levosimendan or Resveratrol offers promising approaches for lung cancer therapy, potentially reducing the need for higher doses of 5-FU and minimizing associated toxicity. Future studies are warranted to elucidate the mechanisms underlying these interactions and assess their clinical relevance.<\/jats:p>","DOI":"10.3390\/app14219658","type":"journal-article","created":{"date-parts":[[2024,10,22]],"date-time":"2024-10-22T11:31:57Z","timestamp":1729596717000},"page":"9658","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Novel Drug Combinations in Lung Cancer: New Potential Synergies Between 5-FU and Repurposed Drugs"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-5370-9586","authenticated-orcid":false,"given":"Eduarda","family":"Ribeiro","sequence":"first","affiliation":[{"name":"OncoPharma Research Group, Center of Health Technology and Services Research (CINTESIS), Rua Doutor Pl\u00e1cido da Costa, 4200-450 Porto, Portugal"},{"name":"CINTESIS@RISE, Faculty of Medicine, University of Porto, Alameda Professor Hern\u00e2ni Monteiro, 4200-319 Porto, Portugal"},{"name":"Intitute os Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1283-1042","authenticated-orcid":false,"given":"Nuno","family":"Vale","sequence":"additional","affiliation":[{"name":"OncoPharma Research Group, Center of Health Technology and Services Research (CINTESIS), Rua Doutor Pl\u00e1cido da Costa, 4200-450 Porto, Portugal"},{"name":"CINTESIS@RISE, Faculty of Medicine, University of Porto, Alameda Professor Hern\u00e2ni Monteiro, 4200-319 Porto, Portugal"},{"name":"Department of Community Medicine, Health Information and Decision (MEDCIDS), Faculty of Medicine, University of Porto, Rua Doutor Pl\u00e1cido da Costa, 4200-450 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"10479","DOI":"10.1007\/s13277-016-4930-4","article-title":"Frequencies of EGFR single nucleotide polymorphisms in non-small cell lung cancer patients and healthy individuals in the Republic of Serbia: A preliminary study","volume":"37","author":"Perin","year":"2016","journal-title":"Tumour Biol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1007\/s10555-010-9209-4","article-title":"Biological and clinical significance of KRAS mutations in lung cancer: An oncogenic driver that contrasts with EGFR mutation","volume":"29","author":"Suda","year":"2010","journal-title":"Cancer Metastasis Rev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1775","DOI":"10.3892\/ol.2015.3414","article-title":"Ethnicity affects EGFR and KRAS gene alterations of lung adenocarcinoma","volume":"10","author":"Soh","year":"2015","journal-title":"Oncol. 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