{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T12:23:36Z","timestamp":1775478216044,"version":"3.50.1"},"reference-count":45,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2022,3,26]],"date-time":"2022-03-26T00:00:00Z","timestamp":1648252800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia","doi-asserted-by":"publisher","award":["SFRH\/BPD\/122871\/2016"],"award-info":[{"award-number":["SFRH\/BPD\/122871\/2016"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Programa Operacional Regional do Norte and co-funded by European Regional Development Fund","award":["NORTE-01-0145-FEDER-072678 -"],"award-info":[{"award-number":["NORTE-01-0145-FEDER-072678 -"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Pirfenidone, an antifibrotic drug, has antitumor potential against different types of cancers. Our work explored whether pirfenidone sensitizes non-small cell lung cancer (NSCLC) cell lines to chemotherapeutic treatments. The cytotoxic effect of paclitaxel in combination with pirfenidone against three NSCLC cell lines (A549, NCI-H322 and NCI-H460) was evaluated using the sulforhodamine B assay. The effects of this combination on cell viability (trypan blue exclusion assay), proliferation (BrdU incorporation assay), cell cycle (flow cytometry following PI staining) and cell death (Annexin V-FITC detection assay and Western blot) were analyzed on the most sensitive cell line (NCI-H460). The cytotoxic effect of this drug combination was also evaluated against two non-tumorigenic cell lines (MCF-10A and MCF-12A). Finally, the ability of pirfenidone to sensitize NCI-H460 cells to a combination of paclitaxel plus carboplatin was assessed. The results demonstrated that pirfenidone sensitized NCI-H460 cells to paclitaxel treatment, reducing cell growth, viability and proliferation, inducing alterations in the cell cycle profile and causing an increase in the % of cell death. Remarkably, this combination did not increase cytotoxicity in non-tumorigenic cells. Importantly, pirfenidone also sensitized NCI-H460 cells to paclitaxel plus carboplatin. This work highlights the possibility of repurposing pirfenidone in combination with chemotherapy for the treatment of NSCLC.<\/jats:p>","DOI":"10.3390\/ijms23073631","type":"journal-article","created":{"date-parts":[[2022,3,27]],"date-time":"2022-03-27T21:27:51Z","timestamp":1648416471000},"page":"3631","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Pirfenidone Sensitizes NCI-H460 Non-Small Cell Lung Cancer Cells to Paclitaxel and to a Combination of Paclitaxel with Carboplatin"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1115-6839","authenticated-orcid":false,"given":"Helena","family":"Branco","sequence":"first","affiliation":[{"name":"i3S\u2014Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, University of Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal"},{"name":"Cancer Drug Resistance Group, IPATIMUP\u2014Institute of Molecular Pathology and Immunology, University of Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9576-3486","authenticated-orcid":false,"given":"J\u00falio","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Experimental Pathology and Therapeutics Group, IPO\u2014Instituto Portugu\u00eas de Oncologia, Rua Dr. Ant\u00f3nio Bernardino de Almeida 865, 4200-072 Porto, Portugal"}]},{"given":"Catarina","family":"Antunes","sequence":"additional","affiliation":[{"name":"i3S\u2014Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, University of Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal"},{"name":"Cancer Drug Resistance Group, IPATIMUP\u2014Institute of Molecular Pathology and Immunology, University of Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal"}]},{"given":"L\u00facio L.","family":"Santos","sequence":"additional","affiliation":[{"name":"Experimental Pathology and Therapeutics Group, IPO\u2014Instituto Portugu\u00eas de Oncologia, Rua Dr. Ant\u00f3nio Bernardino de Almeida 865, 4200-072 Porto, Portugal"},{"name":"ICBAS-UP\u2014School of Medicine and Biomedical Sciences, University of Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7801-4643","authenticated-orcid":false,"given":"Maria Helena","family":"Vasconcelos","sequence":"additional","affiliation":[{"name":"i3S\u2014Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, University of Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal"},{"name":"Cancer Drug Resistance Group, IPATIMUP\u2014Institute of Molecular Pathology and Immunology, University of Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal"},{"name":"Department of Biological Sciences, FFUP\u2014Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4613-1917","authenticated-orcid":false,"given":"Cristina P. R.","family":"Xavier","sequence":"additional","affiliation":[{"name":"i3S\u2014Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, University of Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal"},{"name":"Cancer Drug Resistance Group, IPATIMUP\u2014Institute of Molecular Pathology and Immunology, University of Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J. 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