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Title: 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.
Authors: Navarro-Villarán, Elena
Tinoco, José
Jiménez, Granada
Pereira, Sheila
Wang, Jize
Aliseda, Sara
Rodríguez-Hernández, María A
González, Raúl
Marín-Gómez, Luís M
Gómez-Bravo, Miguel A
Padillo, Francisco J
Álamo-Martínez, José M
Muntané, Jordi
metadata.dc.subject.mesh: Animals
Carcinoma, Hepatocellular
Cell Cycle
Cell Differentiation
Cell Line, Tumor
Cell Proliferation
Enzyme Inhibitors
Immunosuppressive Agents
Liver Neoplasms
Neovascularization, Pathologic
TOR Serine-Threonine Kinases
Xenograft Model Antitumor Assays
Issue Date: 12-Aug-2016
Abstract: Orthotopic 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 Everolimus (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 G0/G1 cell accumulation occurred as a consequence of drastic reduction in S, as well as in S and G2+M phases, respectively. The in vivo studies support data on the more effective antitumoral 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.
metadata.dc.identifier.doi: 10.1371/journal.pone.0160979
Appears in Collections:Producción 2020

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