Potential New Therapeutic Approaches for Cisplatin-Resistant Testicular Germ Cell Tumors

BACKGROUNDTesticular germ cell tumors (TGCTs), a group of heterogeneous neoplasms, are the most frequent tumors of teenagers and young men, with the incidence rising worldwide. High cure rates can be achieved through cisplatin (CDDP)-based treatment, but approximately 10% of patients present refract...

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Published in:	Frontiers in bioscience (Landmark. Print) Vol. 27; no. 8; p. 245
Main Authors:	Lengert, André van Helvoort, Pereira, Leticia do Nascimento Braga, Cabral, Eduardo Ramos Martins, Gomes, Izabela Natalia Faria, Jesus, Lais Machado de, Gonçalves, Maria Fernanda Santiago, Rocha, Aline Oliveira da, Tassinari, Tiago Alexandre, Silva, Luciane Sussuchi da, Laus, Ana Carolina, Vidal, Daniel Onofre, Pinto, Mariana Tomazini, Reis, Rui Manuel, Lopes, Luiz Fernando
Format:	Journal Article
Language:	English
Published:	IMR Press 16-08-2022
Subjects:	cisplatin resistance mg-132 testicular germ-cell tumor
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Summary:	BACKGROUNDTesticular germ cell tumors (TGCTs), a group of heterogeneous neoplasms, are the most frequent tumors of teenagers and young men, with the incidence rising worldwide. High cure rates can be achieved through cisplatin (CDDP)-based treatment, but approximately 10% of patients present refractory disease and virtually no treatment alternatives. Here, we explored new strategies to treat CDDP-resistant. METHODSIn vitro TGCT CDDP-resistance model was established and differential mRNA expression profiles were evaluated using NanoString technology. Then, TGCT cell lines were treated with four potential drugs (PCNA-I1, ML323, T2AA, and MG-132) to overcome CDDP-resistance. RESULTSWe found several differentially expressed genes related to DNA repair and cell cycle regulation on CDDP-resistant cell line (NTERA-2R) compared to parental cell line (NTERA-2P), and the proteasome inhibitor MG-132 demonstrated cytotoxic activity in all cell lines evaluated, even at a nanomolar range. MG-132 also enhanced cell lines' sensitivity to CDDP, increasing apoptosis in both NTERA-2P and NTERA-2R. CONCLUSIONSMG-132 emerges as a potential new drug to treat CDDP-resistant TGCT. Targeted therapy based on molecular mechanism insights may contribute to overcome acquired chemotherapy CDDP-resistance.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	2768-6701 2768-6698
DOI:	10.31083/j.fbl2708245