Comparison of the therapeutic effects of lobaplatin and carboplatin on retinoblastoma in vitro and in vivo.


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
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

697-706

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Auteurs

Zijun Zhou (Z)

Department of Interventional Radiology and Vascular Anomalies, Guangzhou Women and Children's Medical Center of Guangzhou Medical University, Guangzhou, Guangdong 510627, P.R. China.

Hua Jiang (H)

Department of Interventional Radiology and Vascular Anomalies, Guangzhou Women and Children's Medical Center of Guangzhou Medical University, Guangzhou, Guangdong 510627, P.R. China.

Jiejun Xia (J)

Department of Interventional Radiology and Vascular Anomalies, Guangzhou Women and Children's Medical Center of Guangzhou Medical University, Guangzhou, Guangdong 510627, P.R. China.

Jing Zhang (J)

Department of Interventional Radiology and Vascular Anomalies, Guangzhou Women and Children's Medical Center of Guangzhou Medical University, Guangzhou, Guangdong 510627, P.R. China.

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Classifications MeSH