2020-04-302020-04-302016-08-12Navarro Villarán, E., Tinoco, J., Jiménez, G., Pereira Arenas, S., Wang, J., Aliseda, S.,...,Muntané Relat, J. (2016). Differential Antitumoral Properties and Renal-Associated Tissue Damage Induced by Tacrolimus and Mammalian Target of Rapamycin Inhibitors in Hepatocarcinoma: In Vitro and In Vivo Studies.. Plos One, 11 (8)1932-6203https://hdl.handle.net/11441/96021Orthotopic liver transplantation (OLT) is the recommended treatment for patients at early stages of hepatocarcinoma (HCC) with potential portal hypertension and/or bilirubinemia, but without vascular-associated diseases. The patients are receiving immunosuppressive therapy to reduce graft rejection, but differential side effects have been related to calcineurin and mTOR inhibitor administration regarding tumor recurrence and nephrotoxicity. The in vitro studies showed that Tacrolimus exerted a more potent pro-apoptotic effect than Evero- limus (Huh 7>Hep 3B>HepG2), being sirolimus only active in Hep3B cell line. Tacrolimus and Everolimus exerted potent antiproliferative properties in Huh 7 and Hep3B in which cells Sirolimus was inactive. Interestingly, Tacrolimus- and Everolimus-dependent G 0 /G 1 cell accumulation occurred as a consequence of drastic reduction in S, as well as in S and G 2+M phases, respectively. The in vivo studies support data on the more effective antitu- moral properties of Everolimus, eventual risk of pro-angiogenic tumoral properties and nephrotoxicity of Tacrolimus, and pro-proliferative properties of Sirolimus in tumors developed in nude mice.application/pdf17engAttribution-NonCommercial-NoDerivatives 4.0 Internacionalhttp://creativecommons.org/licenses/by-nc-nd/4.0/In VitroIn VivoOrthotopic liver transplantationRenal-Associatedinfo:eu-repo/semantics/articleinfo:eu-repo/semantics/openAccess10.1371/journal.pone.0160979