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In Vitro Evaluation of Rigosertib Antitumoral and Radiosensitizing Effects against Human Cholangiocarcinoma Cells

Cholangiocarcinoma is the first most common cancer of the biliary tract. To date, surgical resection is the only potentially curative option, but it is possible only for a limited percentage of patients, and in any case survival rate is quite low. Moreover, cholangiocarcinoma is often chemotherapy-r...

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Autores principales: Malacrida, Alessio, Rigolio, Roberta, Celio, Luigi, Damian, Silvia, Cavaletti, Guido, Mazzaferro, Vincenzo, Miloso, Mariarosaria
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8348961/
https://www.ncbi.nlm.nih.gov/pubmed/34360994
http://dx.doi.org/10.3390/ijms22158230
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author Malacrida, Alessio
Rigolio, Roberta
Celio, Luigi
Damian, Silvia
Cavaletti, Guido
Mazzaferro, Vincenzo
Miloso, Mariarosaria
author_facet Malacrida, Alessio
Rigolio, Roberta
Celio, Luigi
Damian, Silvia
Cavaletti, Guido
Mazzaferro, Vincenzo
Miloso, Mariarosaria
author_sort Malacrida, Alessio
collection PubMed
description Cholangiocarcinoma is the first most common cancer of the biliary tract. To date, surgical resection is the only potentially curative option, but it is possible only for a limited percentage of patients, and in any case survival rate is quite low. Moreover, cholangiocarcinoma is often chemotherapy-resistant, and the only drug with a significant benefit for patient’s survival is Gemcitabine. It is necessary to find new drugs or combination therapies to treat nonresectable cholangiocarcinoma and improve the overall survival rate of patients. In this work, we evaluate in vitro the antitumoral effects of Rigosertib, a multi-kinase inhibitor in clinical development, against cholangiocarcinoma EGI-1 cell lines. Rigosertib impairs EGI-1 cell viability in a dose- and time-dependent manner, reversibility is dose-dependent, and significant morphological and nuclear alterations occur. Moreover, Rigosertib induces the arrest of the cell cycle in the G2/M phase, increases autophagy, and inhibits proteasome, cell migration, and invasion. Lastly, Rigosertib shows to be a stronger radiosensitizer than Gemcitabine and 5-Fluorouracil. In conclusion, Rigosertib could be a potential therapeutic option, alone or in combination with radiations, for nonresectable patients with cholangiocarcinoma.
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spelling pubmed-83489612021-08-08 In Vitro Evaluation of Rigosertib Antitumoral and Radiosensitizing Effects against Human Cholangiocarcinoma Cells Malacrida, Alessio Rigolio, Roberta Celio, Luigi Damian, Silvia Cavaletti, Guido Mazzaferro, Vincenzo Miloso, Mariarosaria Int J Mol Sci Article Cholangiocarcinoma is the first most common cancer of the biliary tract. To date, surgical resection is the only potentially curative option, but it is possible only for a limited percentage of patients, and in any case survival rate is quite low. Moreover, cholangiocarcinoma is often chemotherapy-resistant, and the only drug with a significant benefit for patient’s survival is Gemcitabine. It is necessary to find new drugs or combination therapies to treat nonresectable cholangiocarcinoma and improve the overall survival rate of patients. In this work, we evaluate in vitro the antitumoral effects of Rigosertib, a multi-kinase inhibitor in clinical development, against cholangiocarcinoma EGI-1 cell lines. Rigosertib impairs EGI-1 cell viability in a dose- and time-dependent manner, reversibility is dose-dependent, and significant morphological and nuclear alterations occur. Moreover, Rigosertib induces the arrest of the cell cycle in the G2/M phase, increases autophagy, and inhibits proteasome, cell migration, and invasion. Lastly, Rigosertib shows to be a stronger radiosensitizer than Gemcitabine and 5-Fluorouracil. In conclusion, Rigosertib could be a potential therapeutic option, alone or in combination with radiations, for nonresectable patients with cholangiocarcinoma. MDPI 2021-07-30 /pmc/articles/PMC8348961/ /pubmed/34360994 http://dx.doi.org/10.3390/ijms22158230 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Malacrida, Alessio
Rigolio, Roberta
Celio, Luigi
Damian, Silvia
Cavaletti, Guido
Mazzaferro, Vincenzo
Miloso, Mariarosaria
In Vitro Evaluation of Rigosertib Antitumoral and Radiosensitizing Effects against Human Cholangiocarcinoma Cells
title In Vitro Evaluation of Rigosertib Antitumoral and Radiosensitizing Effects against Human Cholangiocarcinoma Cells
title_full In Vitro Evaluation of Rigosertib Antitumoral and Radiosensitizing Effects against Human Cholangiocarcinoma Cells
title_fullStr In Vitro Evaluation of Rigosertib Antitumoral and Radiosensitizing Effects against Human Cholangiocarcinoma Cells
title_full_unstemmed In Vitro Evaluation of Rigosertib Antitumoral and Radiosensitizing Effects against Human Cholangiocarcinoma Cells
title_short In Vitro Evaluation of Rigosertib Antitumoral and Radiosensitizing Effects against Human Cholangiocarcinoma Cells
title_sort in vitro evaluation of rigosertib antitumoral and radiosensitizing effects against human cholangiocarcinoma cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8348961/
https://www.ncbi.nlm.nih.gov/pubmed/34360994
http://dx.doi.org/10.3390/ijms22158230
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