{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T02:14:42Z","timestamp":1760235282821,"version":"build-2065373602"},"reference-count":34,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2021,8,6]],"date-time":"2021-08-06T00:00:00Z","timestamp":1628208000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Animals"],"abstract":"<jats:p>Drug repurposing and drug combination are important therapeutic approaches in cancer therapy. Drug repurposing aims to give new indications to drugs, rather than the original indication, whereas drug combination presupposes that the effect that is obtained should be more beneficial than the effect obtained by the individual drugs. Previously, drug repurposing and the combination of different drugs was evaluated in our research group against human breast cancer cells (MCF-7 cells). Our results demonstrated that the response obtained through the combination of drugs, when compared with the single drugs, led to more synergic responses. Therefore, using potential drugs for repurposing, combined with a reference drug in breast cancer (5-Fluorouracil), was the major aim of this project, but for the first time using the feline mammary carcinoma cell line, FMCm. Surprisingly, the feline neoplastic cells demonstrated considerable resistance to the drugs tested in isolation, and the combination was not effective, which contrasted with the obtained MCF-7 cells\u2019 response.<\/jats:p>","DOI":"10.3390\/ani11082321","type":"journal-article","created":{"date-parts":[[2021,8,6]],"date-time":"2021-08-06T08:01:42Z","timestamp":1628236902000},"page":"2321","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["High Drug Resistance in Feline Mammary Carcinoma Cell Line (FMCm) and Comparison with Human Breast Cancer Cell Line (MCF-7)"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8231-1560","authenticated-orcid":false,"given":"Ana Salom\u00e9","family":"Correia","sequence":"first","affiliation":[{"name":"OncoPharma Research Group, Center for Health Technology and Services Research (CINTESIS), Rua Dr. Pl\u00e1cido da Costa, 4200-450 Porto, Portugal"},{"name":"Department of Molecular Pathology and Immunology, Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9186-3711","authenticated-orcid":false,"given":"Rita","family":"Matos","sequence":"additional","affiliation":[{"name":"Department of Molecular Pathology and Immunology, Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal"},{"name":"Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Rua J\u00falio Amaral de Carvalho 45, 4200-135 Porto, Portugal"},{"name":"i3S, Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade da Universidade do Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5302-0086","authenticated-orcid":false,"given":"F\u00e1tima","family":"G\u00e4rtner","sequence":"additional","affiliation":[{"name":"Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Rua J\u00falio Amaral de Carvalho 45, 4200-135 Porto, Portugal"},{"name":"i3S, Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade da Universidade do Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2305-1631","authenticated-orcid":false,"given":"Irina","family":"Amorim","sequence":"additional","affiliation":[{"name":"Department of Molecular Pathology and Immunology, Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal"},{"name":"Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Rua J\u00falio Amaral de Carvalho 45, 4200-135 Porto, Portugal"},{"name":"i3S, Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade da Universidade do Porto, Rua Alfredo Allen 208, 4200-135 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), Rua Dr. Pl\u00e1cido da Costa, 4200-450 Porto, Portugal"},{"name":"Department of Community Medicine, Health Information and Decision (MEDCIDS), Faculty of Medicine, University of Porto, Al. Prof. Hern\u00e2ni Monteiro, 4200-319 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"477","DOI":"10.24272\/j.issn.2095-8137.2020.095","article-title":"Breast cancer animal models and applications","volume":"41","author":"Zeng","year":"2020","journal-title":"Zool. Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3882","DOI":"10.7150\/thno.55760","article-title":"Molecular targets for anticancer therapies in companion animals and humans: What can we learn from each other?","volume":"11","author":"Kromhout","year":"2021","journal-title":"Theranostics"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1017\/S0022029905001263","article-title":"Feline mammary tumours in comparative oncology","volume":"72","author":"Zappulli","year":"2005","journal-title":"J. Dairy Res."},{"key":"ref_4","unstructured":"(2021, May 27). Feline Mammary Tumors|Veterinary Medical Center. Available online: https:\/\/vet.osu.edu\/vmc\/companion\/our-services\/oncology-and-hematology\/common-tumor-types\/feline-mammary-tumors."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Almeida, F., Gameiro, A., Correia, J., and Ferreira, F. (2021). Histone Deacetylase Inhibitors and Microtubule Inhibitors Induce Apoptosis in Feline Luminal Mammary Carcinoma Cells. Animals, 11.","DOI":"10.3390\/ani11020502"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Figueira, A.C., Gomes, C., Mendes, N., Amorim, I., De Matos, A.J.F., Dias-Pereira, P., and G\u00e4rtner, F. (2016). An in vitro and in vivo characterization of the cadherin-catenin adhesion complex in a feline mammary carcinoma cell line. Clin. Diagn. Pathol., 1.","DOI":"10.15761\/NRD.1000103"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Correia, A., Silva, D., Correia, A., Vilanova, M., G\u00e4rtner, F., and Vale, N. (2018). Study of new therapeutic strategies to combat breast cancer using drug combinations. Biomolecules, 8.","DOI":"10.3390\/biom8040175"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1186\/s12967-016-1031-5","article-title":"Repurposing of approved cardiovascular drugs","volume":"14","author":"Ishida","year":"2016","journal-title":"J. Transl. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"732","DOI":"10.1038\/nrclinonc.2015.169","article-title":"Drug repurposing in oncology\u2014Patient and health systems opportunities","volume":"12","author":"Bertolini","year":"2015","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1038\/nbt.3834","article-title":"Synergistic drug combinations for cancer identified in a CRISPR screen for pairwise genetic interactions","volume":"35","author":"Han","year":"2017","journal-title":"Nat. Biotechnol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1002\/prp2.149","article-title":"Analysis of drug combinations: Current methodological landscape","volume":"3","author":"Foucquier","year":"2015","journal-title":"Pharmacol. Res. Perspect."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1038\/nrd2683","article-title":"Mechanisms of drug combinations: Interaction and network perspectives","volume":"8","author":"Jia","year":"2009","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_13","unstructured":"(2021, May 27). Comprehensive Cancer Information-National Cancer Institute, Available online: https:\/\/www.cancer.gov\/."},{"key":"ref_14","unstructured":"(2021, July 23). DrugBank Online|Database for Drug and Drug Target Info. Available online: https:\/\/go.drugbank.com\/."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.bbrc.2019.05.189","article-title":"Synergistic effect of paclitaxel and verapamil to overcome multi-drug resistance in breast cancer cells","volume":"516","author":"Li","year":"2019","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"30252","DOI":"10.18632\/oncotarget.16325","article-title":"Aspirin regulation of c-myc and cyclinD1 proteins to overcome tamoxifen resistance in estrogen receptor-positive breast cancer cells","volume":"8","author":"Cheng","year":"2017","journal-title":"Oncotarget"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"18640","DOI":"10.18632\/oncotarget.15553","article-title":"The angiotensin receptor blocker, Losartan, inhibits mammary tumor development and progression to invasive carcinoma","volume":"8","author":"Coulson","year":"2017","journal-title":"Oncotarget"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1016\/j.ejphar.2019.05.017","article-title":"Chloroquine inhibits tumor-related Kv10.1 channel and decreases migration of MDA-MB-231 breast cancer cells in vitro","volume":"855","year":"2019","journal-title":"Eur. J. Pharmacol."},{"key":"ref_19","unstructured":"(2021, July 23). Neoplasma. Available online: http:\/\/www.elis.sk\/index.php?page=shop.product_details&flypage=flypage.tpl&product_id=889&category_id=31&option=com_virtuemart&vmcchk=1&Itemid=1."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.canlet.2016.10.034","article-title":"Anti-proliferation of breast cancer cells with itraconazole: Hedgehog pathway inhibition induces apoptosis and autophagic cell death","volume":"385","author":"Wang","year":"2017","journal-title":"Cancer Lett."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1039\/C8BM01189C","article-title":"Repurposing antitubercular agent isoniazid for treatment of prostate cancer","volume":"7","author":"Lv","year":"2018","journal-title":"Biomater. Sci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1080\/07357900701874658","article-title":"Statin-induced inhibition of MCF-7 breast cancer cell proliferation is related to cell cycle arrest and apoptotic and necrotic cell death mediated by an enhanced oxidative stress","volume":"26","author":"Rodriguez","year":"2008","journal-title":"Cancer Investig."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Silva, S., Alves, C., Duarte, D., Costa, A., Sarmento, B., Almeida, A.J., Gomes, P., and Vale, N. (2020). Model Amphipathic Peptide Coupled with Tacrine to Improve Its Antiproliferative Activity. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22010242"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1273","DOI":"10.1292\/jvms.67.1273","article-title":"Establishment and characterization of eight feline mammary adenocarcinoma cell lines","volume":"67","author":"Uyama","year":"2005","journal-title":"J. Vet. Med. Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1038\/nrc1074","article-title":"5-Fluorouracil: Mechanisms of action and clinical strategies","volume":"3","author":"Longley","year":"2003","journal-title":"Nat. Rev. Cancer"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1177\/0300985816650243","article-title":"Feline Mammary Cancer: Novel Nude Mouse Model and Molecular Characterization of Invasion and Metastasis Genes","volume":"54","author":"Hassan","year":"2017","journal-title":"Vet. Pathol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1038\/onc.2009.338","article-title":"Extracellular cleavage and shedding of P-cadherin: A mechanism underlying the invasive behaviour of breast cancer cells","volume":"29","author":"Ribeiro","year":"2010","journal-title":"Oncogene"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1002\/path.4143","article-title":"P-cadherin functional role is dependent on E-cadherin cellular context: A proof of concept using the breast cancer model","volume":"229","author":"Ribeiro","year":"2013","journal-title":"J. Pathol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/j.intimp.2016.11.027","article-title":"Chloroquine (CQ) exerts anti-breast cancer through modulating microenvironment and inducing apoptosis","volume":"42","author":"Zhang","year":"2017","journal-title":"Int. Immunopharmacol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"215","DOI":"10.2165\/00003088-198916040-00002","article-title":"Clinical Pharmacology of 5-Fluorouracil","volume":"16","author":"Diasio","year":"1989","journal-title":"Clin. Pharmacokinet."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1002\/jcp.1041040305","article-title":"Facilitated transport of uracil and 5-fluorouracil, and permeation of orotic acid into cultured mammalian cells","volume":"104","author":"Wohlhueter","year":"1980","journal-title":"J. Cell. Physiol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12943-015-0448-4","article-title":"P-cadherin and the journey to cancer metastasis","volume":"14","author":"Vieira","year":"2015","journal-title":"Mol. Cancer"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"4769","DOI":"10.1038\/s41388-018-0304-2","article-title":"E-cadherin in contact inhibition and cancer","volume":"37","author":"Mendonsa","year":"2018","journal-title":"Oncogene"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Verbaanderd, C., Maes, H., Schaaf, M.B., Sukhatme, V.P., Pantziarka, P., Sukhatme, V., Agostinis, P., and Bouche, G. (2017). Repurposing Drugs in Oncology (ReDO)\u2014chloroquine and hydroxychloroquine as anti-cancer agents. Ecancermedicalscience, 11.","DOI":"10.3332\/ecancer.2017.781"}],"container-title":["Animals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-2615\/11\/8\/2321\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:41:35Z","timestamp":1760164895000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-2615\/11\/8\/2321"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,6]]},"references-count":34,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2021,8]]}},"alternative-id":["ani11082321"],"URL":"https:\/\/doi.org\/10.3390\/ani11082321","relation":{},"ISSN":["2076-2615"],"issn-type":[{"type":"electronic","value":"2076-2615"}],"subject":[],"published":{"date-parts":[[2021,8,6]]}}}