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Monocarboxylate transporters (MCTs) are crucial to avoid cellular acidosis by internal lactate accumulation, being largely overexpressed by cancer cells and associated with cancer aggressiveness. The MCT1-specific inhibitor AZD3965 has shown encouraging results in different cancer models. However, it has not been tested in urothelial bladder cancer (UBC), a neoplasm where rates of recurrence, progression and platinum-based resistance are generally elevated. We used two muscle-invasive UBC cell lines to study AZD3965 activity regarding lactate production, UBC cells\u2019 viability and proliferation, cell cycle profile, and migration and invasion properties. An \u201cin vivo\u201d assay with the chick chorioallantoic membrane model was additionally performed, as well as the combination of the compound with cisplatin. AZD3965 demonstrated anticancer activity upon low levels of MCT4, while a general lack of sensitivity was observed under MCT4 high expression. Cell viability, proliferation and migration were reduced, cell cycle was arrested, and tumor growth \u201cin vivo\u201d was inhibited. The compound sensitized these MCT4-low-expressing cells to cisplatin. Thus, AZD3965 seems to display anticancer properties in UBC under a low MCT4-expression setting, but additional studies are necessary to confirm AZD3965 activity in this cancer model.<\/jats:p>","DOI":"10.3390\/pharmaceutics15122688","type":"journal-article","created":{"date-parts":[[2023,11,28]],"date-time":"2023-11-28T07:40:01Z","timestamp":1701157201000},"page":"2688","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Effects of Lactate Transport Inhibition by AZD3965 in Muscle-Invasive Urothelial Bladder Cancer"],"prefix":"10.3390","volume":"15","author":[{"given":"Ana","family":"Silva","sequence":"first","affiliation":[{"name":"Life and Health Sciences Research Institute (ICVS), University of Minho, Campus of Gualtar, 4710-057 Braga, Portugal"},{"name":"ICVS\/3B\u2019s\u2014PT Government Associate Laboratory, 4710-057 Braga, Portugal"}]},{"given":"Ana","family":"F\u00e9lix","sequence":"additional","affiliation":[{"name":"Life and Health Sciences Research Institute (ICVS), University of Minho, Campus of Gualtar, 4710-057 Braga, Portugal"},{"name":"ICVS\/3B\u2019s\u2014PT Government Associate Laboratory, 4710-057 Braga, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8167-4140","authenticated-orcid":false,"given":"M\u00f3nica","family":"Cerqueira","sequence":"additional","affiliation":[{"name":"Life and Health Sciences Research Institute (ICVS), University of Minho, Campus of Gualtar, 4710-057 Braga, Portugal"},{"name":"ICVS\/3B\u2019s\u2014PT Government Associate Laboratory, 4710-057 Braga, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3713-119X","authenticated-orcid":false,"given":"C\u00e9line S.","family":"Gon\u00e7alves","sequence":"additional","affiliation":[{"name":"Life and Health Sciences Research Institute (ICVS), University of Minho, Campus of Gualtar, 4710-057 Braga, Portugal"},{"name":"ICVS\/3B\u2019s\u2014PT Government Associate Laboratory, 4710-057 Braga, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6580-0971","authenticated-orcid":false,"given":"Bel\u00e9m","family":"Sampaio-Marques","sequence":"additional","affiliation":[{"name":"Life and Health Sciences Research Institute (ICVS), University of Minho, Campus of Gualtar, 4710-057 Braga, Portugal"},{"name":"ICVS\/3B\u2019s\u2014PT Government Associate Laboratory, 4710-057 Braga, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5779-9752","authenticated-orcid":false,"given":"Adhemar","family":"Longatto-Filho","sequence":"additional","affiliation":[{"name":"Life and Health Sciences Research Institute (ICVS), University of Minho, Campus of Gualtar, 4710-057 Braga, Portugal"},{"name":"ICVS\/3B\u2019s\u2014PT Government Associate Laboratory, 4710-057 Braga, Portugal"},{"name":"Laboratory of Medical Investigation (LIM14), Faculty of Medicine, S\u00e3o Paulo State University, S\u00e3o Paulo 01049-010, SP, Brazil"},{"name":"Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos 14784-400, SP, Brazil"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1770-4544","authenticated-orcid":false,"given":"F\u00e1tima","family":"Baltazar","sequence":"additional","affiliation":[{"name":"Life and Health Sciences Research Institute (ICVS), University of Minho, Campus of Gualtar, 4710-057 Braga, Portugal"},{"name":"ICVS\/3B\u2019s\u2014PT Government Associate Laboratory, 4710-057 Braga, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9748-3752","authenticated-orcid":false,"given":"Julieta","family":"Afonso","sequence":"additional","affiliation":[{"name":"Life and Health Sciences Research Institute (ICVS), University of Minho, Campus of Gualtar, 4710-057 Braga, Portugal"},{"name":"ICVS\/3B\u2019s\u2014PT Government Associate Laboratory, 4710-057 Braga, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2023,11,28]]},"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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