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

doi:10.3892/ol.2022.13512

Effect of the PARP inhibitor veliparib on germ cell tumor cell lines

Authors:
- Silvia Schmidtova
- Natalia Udvorkova
- Zuzana Cierna
- Samuel Horak
- Katarina Kalavska
- Michal Chovanec
- Lucia Rojikova
- Miriam Vulevova
- Lucia Kucerova
- Michal Mego
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Affiliations: Cancer Research Institute, Biomedical Research Center, Slovak Academy of Sciences, 845 05 Bratislava, Slovakia, Department of Pathology, Faculty of Medicine, Comenius University, 811 08 Bratislava, Slovakia, Translational Research Unit, Faculty of Medicine, Comenius University, 833 10 Bratislava, Slovakia, Institute of Pharmacology and Clinical Pharmacology, Faculty of Medicine, Comenius University, 811 08 Bratislava, Slovakia
Published online on: September 21, 2022 https://doi.org/10.3892/ol.2022.13512
Article Number: 392
Copyright: © Schmidtova et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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.

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