Cargando…

Response of the Urothelial Carcinoma Cell Lines to Cisplatin

Cisplatin (CDDP)-based chemotherapy is the standard of care in patients with muscle-invasive bladder cancer. However, in a large number of cases, the disease becomes resistant or does not respond to CDDP, and thus progresses and disseminates. In such cases, prognosis of patients is very poor. CDDP m...

Descripción completa

Detalles Bibliográficos
Autores principales: Holíčková, Andrea, Roška, Jan, Órásová, Eveline, Bruderová, Vladimíra, Palacka, Patrik, Jurkovičová, Dana, Chovanec, Miroslav
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9604399/
https://www.ncbi.nlm.nih.gov/pubmed/36293346
http://dx.doi.org/10.3390/ijms232012488
_version_ 1784817804336168960
author Holíčková, Andrea
Roška, Jan
Órásová, Eveline
Bruderová, Vladimíra
Palacka, Patrik
Jurkovičová, Dana
Chovanec, Miroslav
author_facet Holíčková, Andrea
Roška, Jan
Órásová, Eveline
Bruderová, Vladimíra
Palacka, Patrik
Jurkovičová, Dana
Chovanec, Miroslav
author_sort Holíčková, Andrea
collection PubMed
description Cisplatin (CDDP)-based chemotherapy is the standard of care in patients with muscle-invasive bladder cancer. However, in a large number of cases, the disease becomes resistant or does not respond to CDDP, and thus progresses and disseminates. In such cases, prognosis of patients is very poor. CDDP manifests its cytotoxic effects mainly through DNA damage induction. Hence, response to CDDP is mainly dependent on DNA damage repair and tolerance mechanisms. Herein, we have examined CDDP response in a panel of the urothelial carcinoma cell (UCC) lines. We characterized these cell lines with regard to viability after CDDP treatment, as well as kinetics of induction and repair of CDDP-induced DNA damage. We demonstrate that repair of CDDP-induced DNA lesions correlates, at least to some extent, with CDDP sensitivity. Furthermore, we monitored expression of the key genes involved in selected DNA repair and tolerance mechanisms, nucleotide excision repair, homologous recombination and translesion DNA synthesis, and show that it differs in the UCC lines and positively correlates with CDDP resistance. Our data indicate that CDDP response in the UCC lines is dependent on DNA damage repair and tolerance factors, which may, therefore, represent valuable therapeutic targets in this malignancy.
format Online
Article
Text
id pubmed-9604399
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-96043992022-10-27 Response of the Urothelial Carcinoma Cell Lines to Cisplatin Holíčková, Andrea Roška, Jan Órásová, Eveline Bruderová, Vladimíra Palacka, Patrik Jurkovičová, Dana Chovanec, Miroslav Int J Mol Sci Article Cisplatin (CDDP)-based chemotherapy is the standard of care in patients with muscle-invasive bladder cancer. However, in a large number of cases, the disease becomes resistant or does not respond to CDDP, and thus progresses and disseminates. In such cases, prognosis of patients is very poor. CDDP manifests its cytotoxic effects mainly through DNA damage induction. Hence, response to CDDP is mainly dependent on DNA damage repair and tolerance mechanisms. Herein, we have examined CDDP response in a panel of the urothelial carcinoma cell (UCC) lines. We characterized these cell lines with regard to viability after CDDP treatment, as well as kinetics of induction and repair of CDDP-induced DNA damage. We demonstrate that repair of CDDP-induced DNA lesions correlates, at least to some extent, with CDDP sensitivity. Furthermore, we monitored expression of the key genes involved in selected DNA repair and tolerance mechanisms, nucleotide excision repair, homologous recombination and translesion DNA synthesis, and show that it differs in the UCC lines and positively correlates with CDDP resistance. Our data indicate that CDDP response in the UCC lines is dependent on DNA damage repair and tolerance factors, which may, therefore, represent valuable therapeutic targets in this malignancy. MDPI 2022-10-18 /pmc/articles/PMC9604399/ /pubmed/36293346 http://dx.doi.org/10.3390/ijms232012488 Text en © 2022 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
Holíčková, Andrea
Roška, Jan
Órásová, Eveline
Bruderová, Vladimíra
Palacka, Patrik
Jurkovičová, Dana
Chovanec, Miroslav
Response of the Urothelial Carcinoma Cell Lines to Cisplatin
title Response of the Urothelial Carcinoma Cell Lines to Cisplatin
title_full Response of the Urothelial Carcinoma Cell Lines to Cisplatin
title_fullStr Response of the Urothelial Carcinoma Cell Lines to Cisplatin
title_full_unstemmed Response of the Urothelial Carcinoma Cell Lines to Cisplatin
title_short Response of the Urothelial Carcinoma Cell Lines to Cisplatin
title_sort response of the urothelial carcinoma cell lines to cisplatin
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9604399/
https://www.ncbi.nlm.nih.gov/pubmed/36293346
http://dx.doi.org/10.3390/ijms232012488
work_keys_str_mv AT holickovaandrea responseoftheurothelialcarcinomacelllinestocisplatin
AT roskajan responseoftheurothelialcarcinomacelllinestocisplatin
AT orasovaeveline responseoftheurothelialcarcinomacelllinestocisplatin
AT bruderovavladimira responseoftheurothelialcarcinomacelllinestocisplatin
AT palackapatrik responseoftheurothelialcarcinomacelllinestocisplatin
AT jurkovicovadana responseoftheurothelialcarcinomacelllinestocisplatin
AT chovanecmiroslav responseoftheurothelialcarcinomacelllinestocisplatin