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On the other hand, a better outcome has been related to serum sodium normalization. In vitro studies have shown that low extracellular sodium promotes cancer cells proliferation and invasiveness. Tolvaptan, a selective vasopressin receptor type 2 (V<jats:sub>2<\/jats:sub>) antagonist, has been effectively used in the last decade for the treatment of hyponatremia secondary to the Syndrome of Inappropriate Antidiuresis. A few in vitro data suggested a direct role of tolvaptan in counteracting cancer progression, so far. The aim of this study was to evaluate the effect and the mechanism of action of tolvaptan in cell lines from different tumours [i.e. colon cancer (HCT-8), hepatocarcinoma (HepG2), neuroblastoma (SK-N-AS)].<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods and results<\/jats:title>\n                <jats:p>First, we showed that these cell lines express the V<jats:sub>2<\/jats:sub> receptor. Tolvaptan significantly reduced cell proliferation with an IC<jats:sub>50<\/jats:sub> in the micromolar range. Accordingly, reduced levels of cAMP, of the\u00a0catalytic \u03b1 subunit of PKA, and a reduced pAKT\/AKT ratio were observed. Tolvaptan effectively inhibited cell cycle progression, whereas it induced apoptotis. Furthermore, it reduced cell invasiveness. In particular, anchorage-independent growth and the activity of collagenases type IV were blunted in the three cell lines. Accordingly, tolvaptan counteracted the RhoA\/ROCK1\u20132 pathway, which has a pivotal role in regulating cell movement.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Overall, these findings indicate that tolvaptan effectively inhibits tumour progression in vitro. Further studies should clarify whether the V<jats:sub>2<\/jats:sub> receptor might be considered a possible target in anti-cancer strategies in the future.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s40618-022-01807-5","type":"journal-article","created":{"date-parts":[[2022,5,23]],"date-time":"2022-05-23T09:03:20Z","timestamp":1653296600000},"page":"1693-1708","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["The V2 receptor antagonist tolvaptan counteracts proliferation and invasivity in human cancer cells"],"prefix":"10.1007","volume":"45","author":[{"given":"G.","family":"Marroncini","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Anceschi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Naldi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B.","family":"Fibbi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F.","family":"Baldanzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Maggi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6417-434X","authenticated-orcid":false,"given":"A.","family":"Peri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,5,23]]},"reference":[{"key":"1807_CR1","doi-asserted-by":"publisher","first-page":"222","DOI":"10.1053\/j.ajkd.2011.08.029","volume":"59","author":"SM Doshi","year":"2012","unstructured":"Doshi SM, Shah P, Lei X et al (2012) Hyponatremia in hospitalized cancer patients and its impact on clinical outcomes. 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