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Effect of the PARP inhibitor veliparib on germ cell tumor cell lines
Germ cell tumors (GCTs) usually represent efficiently curable neoplasms due to their chemosensitivity to platinum-based therapeutic regimen. However, some patients develop therapeutic resistance and succumb to their disease. Novel therapeutic approaches are therefore needed for these patients. It ha...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
D.A. Spandidos
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9533362/ https://www.ncbi.nlm.nih.gov/pubmed/36276487 http://dx.doi.org/10.3892/ol.2022.13512 |
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author | Schmidtova, Silvia Udvorkova, Natalia Cierna, Zuzana Horak, Samuel Kalavska, Katarina Chovanec, Michal Rojikova, Lucia Vulevova, Miriam Kucerova, Lucia Mego, Michal |
author_facet | Schmidtova, Silvia Udvorkova, Natalia Cierna, Zuzana Horak, Samuel Kalavska, Katarina Chovanec, Michal Rojikova, Lucia Vulevova, Miriam Kucerova, Lucia Mego, Michal |
author_sort | Schmidtova, Silvia |
collection | PubMed |
description | Germ cell tumors (GCTs) usually represent efficiently curable neoplasms due to their chemosensitivity to platinum-based therapeutic regimen. However, some patients develop therapeutic resistance and succumb to their disease. Novel therapeutic approaches are therefore needed for these patients. It has previously been demonstrated that poly (ADP-ribose) polymerase (PARP) expression is upregulated in GCTs compared with normal testis tissue. Therefore, PARP expression was analyzed in GCT cell lines and xenografts and it was examined whether its inhibition by veliparib can reverse cisplatin-resistance. Its expression was analyzed in sensitive and cisplatin-resistant variants (referred to as CisR throughout the manuscript) GCT cell lines and xenografts using quantitative PCR, western blotting and immunohistochemistry. The present study investigated whether the combination of cisplatin with the PARP inhibitor veliparib increased the cytotoxic effect of cisplatin in vitro using a luminescent viability assay and an immunodeficient mouse model in vivo. PARP expression was observed in all tested cell lines, with the highest expression in embryonal carcinoma (EC) cell lines and xenografts. Low or no expression was detected in the JEG-3 choriocarcinoma cell line pairs and xenografts. The combination of veliparib and cisplatin or carboplatin was examined in the cisplatin-resistant NTERA-2 CisR and NCCIT CisR EC cell lines and synergistic effects were observed in NTERA-2 CisR cells. However, in vivo analysis did not confirm this synergy. The present data indicated PARP expression in GCT cell lines and xenografts. However, veliparib failed to increase the cytotoxicity of platinum-based drugs. Therefore, further research is warranted to effectively inhibit PARP using different PARP inhibitors or other drug combinations. |
format | Online Article Text |
id | pubmed-9533362 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | D.A. Spandidos |
record_format | MEDLINE/PubMed |
spelling | pubmed-95333622022-10-20 Effect of the PARP inhibitor veliparib on germ cell tumor cell lines Schmidtova, Silvia Udvorkova, Natalia Cierna, Zuzana Horak, Samuel Kalavska, Katarina Chovanec, Michal Rojikova, Lucia Vulevova, Miriam Kucerova, Lucia Mego, Michal Oncol Lett Articles Germ cell tumors (GCTs) usually represent efficiently curable neoplasms due to their chemosensitivity to platinum-based therapeutic regimen. However, some patients develop therapeutic resistance and succumb to their disease. Novel therapeutic approaches are therefore needed for these patients. It has previously been demonstrated that poly (ADP-ribose) polymerase (PARP) expression is upregulated in GCTs compared with normal testis tissue. Therefore, PARP expression was analyzed in GCT cell lines and xenografts and it was examined whether its inhibition by veliparib can reverse cisplatin-resistance. Its expression was analyzed in sensitive and cisplatin-resistant variants (referred to as CisR throughout the manuscript) GCT cell lines and xenografts using quantitative PCR, western blotting and immunohistochemistry. The present study investigated whether the combination of cisplatin with the PARP inhibitor veliparib increased the cytotoxic effect of cisplatin in vitro using a luminescent viability assay and an immunodeficient mouse model in vivo. PARP expression was observed in all tested cell lines, with the highest expression in embryonal carcinoma (EC) cell lines and xenografts. Low or no expression was detected in the JEG-3 choriocarcinoma cell line pairs and xenografts. The combination of veliparib and cisplatin or carboplatin was examined in the cisplatin-resistant NTERA-2 CisR and NCCIT CisR EC cell lines and synergistic effects were observed in NTERA-2 CisR cells. However, in vivo analysis did not confirm this synergy. The present data indicated PARP expression in GCT cell lines and xenografts. However, veliparib failed to increase the cytotoxicity of platinum-based drugs. Therefore, further research is warranted to effectively inhibit PARP using different PARP inhibitors or other drug combinations. D.A. Spandidos 2022-09-21 /pmc/articles/PMC9533362/ /pubmed/36276487 http://dx.doi.org/10.3892/ol.2022.13512 Text en Copyright: © Schmidtova et al. https://creativecommons.org/licenses/by-nc-nd/4.0/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 Schmidtova, Silvia Udvorkova, Natalia Cierna, Zuzana Horak, Samuel Kalavska, Katarina Chovanec, Michal Rojikova, Lucia Vulevova, Miriam Kucerova, Lucia Mego, Michal Effect of the PARP inhibitor veliparib on germ cell tumor cell lines |
title | Effect of the PARP inhibitor veliparib on germ cell tumor cell lines |
title_full | Effect of the PARP inhibitor veliparib on germ cell tumor cell lines |
title_fullStr | Effect of the PARP inhibitor veliparib on germ cell tumor cell lines |
title_full_unstemmed | Effect of the PARP inhibitor veliparib on germ cell tumor cell lines |
title_short | Effect of the PARP inhibitor veliparib on germ cell tumor cell lines |
title_sort | effect of the parp inhibitor veliparib on germ cell tumor cell lines |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9533362/ https://www.ncbi.nlm.nih.gov/pubmed/36276487 http://dx.doi.org/10.3892/ol.2022.13512 |
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