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Effects of Sorafenib, a Tyrosin Kinase Inhibitor, on Adrenocortical Cancer

The lack of an effective medical treatment for adrenocortical carcinoma (ACC) has prompted the search for better treatment protocols for ACC neoplasms. Sorafenib, a tyrosine kinase inhibitor has exhibited effectiveness in the treatment of different human tumors. Therefore, the aim of this study was...

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Autores principales: Cerquetti, Lidia, Bucci, Barbara, Raffa, Salvatore, Amendola, Donatella, Maggio, Roberta, Lardo, Pina, Petrangeli, Elisa, Torrisi, Maria Rosaria, Toscano, Vincenzo, Pugliese, Giuseppe, Stigliano, Antonio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8183165/
https://www.ncbi.nlm.nih.gov/pubmed/34108938
http://dx.doi.org/10.3389/fendo.2021.667798
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author Cerquetti, Lidia
Bucci, Barbara
Raffa, Salvatore
Amendola, Donatella
Maggio, Roberta
Lardo, Pina
Petrangeli, Elisa
Torrisi, Maria Rosaria
Toscano, Vincenzo
Pugliese, Giuseppe
Stigliano, Antonio
author_facet Cerquetti, Lidia
Bucci, Barbara
Raffa, Salvatore
Amendola, Donatella
Maggio, Roberta
Lardo, Pina
Petrangeli, Elisa
Torrisi, Maria Rosaria
Toscano, Vincenzo
Pugliese, Giuseppe
Stigliano, Antonio
author_sort Cerquetti, Lidia
collection PubMed
description The lack of an effective medical treatment for adrenocortical carcinoma (ACC) has prompted the search for better treatment protocols for ACC neoplasms. Sorafenib, a tyrosine kinase inhibitor has exhibited effectiveness in the treatment of different human tumors. Therefore, the aim of this study was to understand the mechanism through which sorafenib acts on ACC, especially since treatment with sorafenib alone is sometimes unable to induce a long-lasting antiproliferative effect in this tumor type. The effects of sorafenib were tested on the ACC cell line H295R by evaluating cell viability, apoptosis and VEGF receptor signaling which was assessed by analyzing VE-cadherin and β-catenin complex formation. We also tested sorafenib on an in vitro 3D cell culture model using the same cell line. Apoptosis was observed after sorafenib treatment, and coimmunoprecipitation data suggested that the drug prevents formation VEGFR-VE-cadherin and β-catenin proteins complex. These results were confirmed both by ultrastructural analysis and by a 3D model where we observed a disaggregation of spheres into single cells, which is a crucial event that represents the first step of metastasis. Our findings suggest that although sorafenib induces apoptotic cell death a small portion of cells survive the treatment and have characteristics of a malignancy. Based on our data we recommend against the use of sorafenib in patients with ACC.
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spelling pubmed-81831652021-06-08 Effects of Sorafenib, a Tyrosin Kinase Inhibitor, on Adrenocortical Cancer Cerquetti, Lidia Bucci, Barbara Raffa, Salvatore Amendola, Donatella Maggio, Roberta Lardo, Pina Petrangeli, Elisa Torrisi, Maria Rosaria Toscano, Vincenzo Pugliese, Giuseppe Stigliano, Antonio Front Endocrinol (Lausanne) Endocrinology The lack of an effective medical treatment for adrenocortical carcinoma (ACC) has prompted the search for better treatment protocols for ACC neoplasms. Sorafenib, a tyrosine kinase inhibitor has exhibited effectiveness in the treatment of different human tumors. Therefore, the aim of this study was to understand the mechanism through which sorafenib acts on ACC, especially since treatment with sorafenib alone is sometimes unable to induce a long-lasting antiproliferative effect in this tumor type. The effects of sorafenib were tested on the ACC cell line H295R by evaluating cell viability, apoptosis and VEGF receptor signaling which was assessed by analyzing VE-cadherin and β-catenin complex formation. We also tested sorafenib on an in vitro 3D cell culture model using the same cell line. Apoptosis was observed after sorafenib treatment, and coimmunoprecipitation data suggested that the drug prevents formation VEGFR-VE-cadherin and β-catenin proteins complex. These results were confirmed both by ultrastructural analysis and by a 3D model where we observed a disaggregation of spheres into single cells, which is a crucial event that represents the first step of metastasis. Our findings suggest that although sorafenib induces apoptotic cell death a small portion of cells survive the treatment and have characteristics of a malignancy. Based on our data we recommend against the use of sorafenib in patients with ACC. Frontiers Media S.A. 2021-05-24 /pmc/articles/PMC8183165/ /pubmed/34108938 http://dx.doi.org/10.3389/fendo.2021.667798 Text en Copyright © 2021 Cerquetti, Bucci, Raffa, Amendola, Maggio, Lardo, Petrangeli, Torrisi, Toscano, Pugliese and Stigliano https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Endocrinology
Cerquetti, Lidia
Bucci, Barbara
Raffa, Salvatore
Amendola, Donatella
Maggio, Roberta
Lardo, Pina
Petrangeli, Elisa
Torrisi, Maria Rosaria
Toscano, Vincenzo
Pugliese, Giuseppe
Stigliano, Antonio
Effects of Sorafenib, a Tyrosin Kinase Inhibitor, on Adrenocortical Cancer
title Effects of Sorafenib, a Tyrosin Kinase Inhibitor, on Adrenocortical Cancer
title_full Effects of Sorafenib, a Tyrosin Kinase Inhibitor, on Adrenocortical Cancer
title_fullStr Effects of Sorafenib, a Tyrosin Kinase Inhibitor, on Adrenocortical Cancer
title_full_unstemmed Effects of Sorafenib, a Tyrosin Kinase Inhibitor, on Adrenocortical Cancer
title_short Effects of Sorafenib, a Tyrosin Kinase Inhibitor, on Adrenocortical Cancer
title_sort effects of sorafenib, a tyrosin kinase inhibitor, on adrenocortical cancer
topic Endocrinology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8183165/
https://www.ncbi.nlm.nih.gov/pubmed/34108938
http://dx.doi.org/10.3389/fendo.2021.667798
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