{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,22]],"date-time":"2025-11-22T11:31:02Z","timestamp":1763811062286,"version":"build-2065373602"},"reference-count":138,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2022,12,21]],"date-time":"2022-12-21T00:00:00Z","timestamp":1671580800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fundo Europeu de Desenvolvimento Regional (FEDER) through the COMPETE 2020\u2013Operational Program for Competitiveness and Internationalization (POCI), Portugal 2020 and FCT\/MCTES","award":["POCI 01-0145-FEDER-029503 (PTDC\/MEC-ONC\/29503\/2017)"],"award-info":[{"award-number":["POCI 01-0145-FEDER-029503 (PTDC\/MEC-ONC\/29503\/2017)"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The combination of Carboplatin with Paclitaxel is the mainstay treatment for high-grade serous carcinoma; however, many patients with advanced disease undergo relapse due to chemoresistance. Drug repurposing coupled with a combination of two or more compounds with independent mechanisms of action has the potential to increase the success rate of the antineoplastic treatment. The purpose of this study was to explore whether the combination of Carboplatin with repurposed drugs led to a therapeutic benefit. Hence, we assessed the cytotoxic effects of Carboplatin alone and in combination with several repurposed drugs (Pitavastatin, Metformin, Ivermectin, Itraconazole and Alendronate) in two tumoral models, i.e., Carboplatin (OVCAR8) and Carboplatin-Paclitaxel (OVCAR8 PTX R P) chemoresistant cell lines and in a non-tumoral (HOSE6.3) cell line. Cellular viability was measured using the Presto Blue assay, and the synergistic interactions were evaluated using the Chou\u2013Talalay, Bliss Independence and Highest Single Agent reference models. Combining Carboplatin with Pitavastatin or Metformin displayed the highest cytotoxic effect and the strongest synergism among all combinations for OVCAR8 PTX R P cells, resulting in a chemotherapeutic effect superior to Carboplatin as a single agent. Concerning HOSE6.3 cells, combining Carboplatin with almost all the repurposed drugs demonstrated a safe pharmacological profile. Overall, we propose that Pitavastatin or Metformin could act synergistically in combination with Carboplatin for the management of high-grade serous carcinoma patients with a Carboplatin plus Paclitaxel resistance profile.<\/jats:p>","DOI":"10.3390\/ijms24010097","type":"journal-article","created":{"date-parts":[[2022,12,21]],"date-time":"2022-12-21T06:11:24Z","timestamp":1671603084000},"page":"97","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["The Antineoplastic Effect of Carboplatin Is Potentiated by Combination with Pitavastatin or Metformin in a Chemoresistant High-Grade Serous Carcinoma Cell Line"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4733-5778","authenticated-orcid":false,"given":"Mariana","family":"Nunes","sequence":"first","affiliation":[{"name":"Differentiation and Cancer Group, Institute for Research and Innovation in Health (i3S) of the University of Porto, 4200-135 Porto, Portugal"},{"name":"Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1420-5042","authenticated-orcid":false,"given":"Diana","family":"Duarte","sequence":"additional","affiliation":[{"name":"OncoPharma Research Group, Center for Health Technology and Services Research (CINTESIS), 4200-450 Porto, Portugal"},{"name":"Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal"},{"name":"CINTESIS@RISE, Faculty of Medicine, University of Porto, 4200-319 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 for Health Technology and Services Research (CINTESIS), 4200-450 Porto, Portugal"},{"name":"CINTESIS@RISE, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal"},{"name":"Department of Community Medicine, Health Information and Decision (MEDCIDS), Faculty of Medicine, University of Porto, 4200-450 Porto, Portugal"}]},{"given":"Sara","family":"Ricardo","sequence":"additional","affiliation":[{"name":"Differentiation and Cancer Group, Institute for Research and Innovation in Health (i3S) of the University of Porto, 4200-135 Porto, Portugal"},{"name":"Toxicology Research Unit (TOXRUN), University Institute of Health Sciences, Polytechnic and University Cooperative (CESPU), 4585-116 Gandra, Portugal"},{"name":"Department of Pathology, Faculty of Medicine, University of Porto (FMUP), 4200-319 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"133s","DOI":"10.1200\/JCO.2003.01.066","article-title":"Current status of taxane and platinum-based chemotherapy in ovarian cancer","volume":"21","author":"McGuire","year":"2003","journal-title":"J. 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