Comparison of the therapeutic effects of lobaplatin and carboplatin on retinoblastoma in vitro and in vivo.
Animals
Antineoplastic Agents
/ pharmacology
Apoptosis
/ drug effects
Carboplatin
/ pharmacology
Cell Cycle
/ drug effects
Cell Line, Tumor
Cyclin-Dependent Kinase 2
/ genetics
Cyclobutanes
/ pharmacology
E2F1 Transcription Factor
/ genetics
Gene Expression Regulation, Neoplastic
/ drug effects
Humans
Mice, Inbred BALB C
Organoplatinum Compounds
/ pharmacology
Retinal Neoplasms
/ drug therapy
Retinoblastoma
/ drug therapy
Xenograft Model Antitumor Assays
cdc25 Phosphatases
/ genetics
lobaplatin
carboplatin
retinoblastoma
therapeutic effects
Journal
International journal of oncology
ISSN: 1791-2423
Titre abrégé: Int J Oncol
Pays: Greece
ID NLM: 9306042
Informations de publication
Date de publication:
09 2020
09 2020
Historique:
received:
28
09
2019
accepted:
21
05
2020
pubmed:
26
6
2020
medline:
8
6
2021
entrez:
26
6
2020
Statut:
ppublish
Résumé
Retinoblastoma (RB) is one of the most aggressive malignancies affecting infants and children. Platinum drugs are commonly used in the treatment of RB; however, their efficacy is often compromised by drug resistance and severe toxicity. The present study aimed to investigate and compare the toxicity and antitumor activity of the third‑generation platinum drugs, carboplatin and lobaplatin, in vitro and in vivo. The Y79 RB cell line was treated with carboplatin or lobaplatin in vitro and then used to establish xenografts in immunodeficient nude mice in vivo; the effects of pharmacological doses of these drugs were then assessed. High concentrations of carboplatin and lobaplatin markedly inhibited Y79 RB cell proliferation in vitro. In addition, the lobaplatin group exhibited higher proportions of early‑stage apoptotic cells than the carboplatin group, while no significant differences in the proportions of cells in the S phase were observed between the 2 groups, as shown by flow cytometry. Significant changes in the E2F1/Cdc25a/Cdk2 pathway in the RB cells were detected by RNA‑seq following carboplatin or lobaplatin intervention. RT‑qPCR, immunofluorescence and immunohistochemical analyses in vivo and in vitro demonstrated that the trends of drug‑induced inhibition of tumor pathological changes may have been regulated through the E2F1/Cdc25a/Cdk2 pathway, and that lobaplatin was more effective than carboplatin in controlling tumors in vivo. On the whole, the findings of the present study demonstrate that lobaplatin is associated with lower cytotoxicity and exerts more prominent therapeutic effects than carboplatin on Y79 RB cells in vitro and in mice in vivo.
Identifiants
pubmed: 32582992
doi: 10.3892/ijo.2020.5085
pmc: PMC7384850
doi:
Substances chimiques
Antineoplastic Agents
0
Cyclobutanes
0
E2F1 Transcription Factor
0
E2F1 protein, human
0
Organoplatinum Compounds
0
Carboplatin
BG3F62OND5
CDK2 protein, human
EC 2.7.11.22
Cyclin-Dependent Kinase 2
EC 2.7.11.22
CDC25A protein, human
EC 3.1.3.48
cdc25 Phosphatases
EC 3.1.3.48
lobaplatin
OX5XK1JD8C
Types de publication
Comparative Study
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
697-706Références
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