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

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...

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Autores principales: Zhou, Zijun, Jiang, Hua, Xia, Jiejun, Zhang, Jing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7384850/
https://www.ncbi.nlm.nih.gov/pubmed/32582992
http://dx.doi.org/10.3892/ijo.2020.5085
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author Zhou, Zijun
Jiang, Hua
Xia, Jiejun
Zhang, Jing
author_facet Zhou, Zijun
Jiang, Hua
Xia, Jiejun
Zhang, Jing
author_sort Zhou, Zijun
collection PubMed
description 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.
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spelling pubmed-73848502020-07-30 Comparison of the therapeutic effects of lobaplatin and carboplatin on retinoblastoma in vitro and in vivo Zhou, Zijun Jiang, Hua Xia, Jiejun Zhang, Jing Int J Oncol Articles 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. D.A. Spandidos 2020-06-22 /pmc/articles/PMC7384850/ /pubmed/32582992 http://dx.doi.org/10.3892/ijo.2020.5085 Text en Copyright: © Zhou et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Articles
Zhou, Zijun
Jiang, Hua
Xia, Jiejun
Zhang, Jing
Comparison of the therapeutic effects of lobaplatin and carboplatin on retinoblastoma in vitro and in vivo
title Comparison of the therapeutic effects of lobaplatin and carboplatin on retinoblastoma in vitro and in vivo
title_full Comparison of the therapeutic effects of lobaplatin and carboplatin on retinoblastoma in vitro and in vivo
title_fullStr Comparison of the therapeutic effects of lobaplatin and carboplatin on retinoblastoma in vitro and in vivo
title_full_unstemmed Comparison of the therapeutic effects of lobaplatin and carboplatin on retinoblastoma in vitro and in vivo
title_short Comparison of the therapeutic effects of lobaplatin and carboplatin on retinoblastoma in vitro and in vivo
title_sort comparison of the therapeutic effects of lobaplatin and carboplatin on retinoblastoma in vitro and in vivo
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7384850/
https://www.ncbi.nlm.nih.gov/pubmed/32582992
http://dx.doi.org/10.3892/ijo.2020.5085
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