Response of the Urothelial Carcinoma Cell Lines to Cisplatin.
DNA damage repair and tolerance
bladder cancer
cisplatin
homologous recombination
nucleotide excision repair
translesion DNA synthesis
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
18 Oct 2022
18 Oct 2022
Historique:
received:
09
08
2022
revised:
15
10
2022
accepted:
16
10
2022
entrez:
27
10
2022
pubmed:
28
10
2022
medline:
29
10
2022
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 36293346
pii: ijms232012488
doi: 10.3390/ijms232012488
pmc: PMC9604399
pii:
doi:
Substances chimiques
Cisplatin
Q20Q21Q62J
Antineoplastic Agents
0
DNA
9007-49-2
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : VEGA Grant Agency of the Slovak Republic
ID : 2/0053/19
Organisme : Slovak Research and Development Agency
ID : APVV-19-0286
Organisme : Ministry of Health of the Slovak Republic
ID : 2019/57-BMCSAV-1
Organisme : Ministry of Education, Science Research and Sport of the Slovak Republic
ID : MVTS 34097104
Organisme : Integrated Infrastructure Operational Program for the projects "Systemic public research infrastructure - biobank for cancer and rare diseases"
ID : ITMS: 313011AFG5
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