IMR Press / FBL / Volume 27 / Issue 8 / DOI: 10.31083/j.fbl2708245
Open Access Original Research
Potential New Therapeutic Approaches for Cisplatin-Resistant Testicular Germ Cell Tumors
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1 Molecular Oncology Research Center, Barretos Cancer Hospital, 14784400 Barretos, Sao Paulo, Brazil
2 Brazilian Childhood Germ Cell Tumor Study Group, from the Brazilian Pediatric Oncology Society (SOBOPE), 14784400 Barretos, São Paulo, Brazil
3 Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, 4710057 Braga, Portugal
4 ICVS/3B's - PT Government Associate Laboratory, 4806909 Braga/Guimaraes, Portugal
5 Barretos Children’s Cancer Hospital from Hospital de Amor, 14784400 Barretos, São Paulo, Brazil
*Correspondence: ahlengert@gmail.com (André van Helvoort Lengert); lf.lopes@yahoo.com (Luiz Fernando Lopes)
Academic Editors: Simona Daniele and Rebecca Piccarducci
Front. Biosci. (Landmark Ed) 2022, 27(8), 245; https://doi.org/10.31083/j.fbl2708245
Submitted: 19 April 2022 | Revised: 9 June 2022 | Accepted: 13 June 2022 | Published: 16 August 2022
Copyright: © 2022 The Author(s). Published by IMR Press.

This is an open access article under the CC BY 4.0 license.

Abstract

Background: Testicular 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. Methods: In 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. Results: We 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. Conclusions: MG-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.

Keywords
testicular germ-cell tumor
cisplatin resistance
MG-132
Figures
Fig. 1.
Funding
2017/22305-9/ Sao Paulo Research Foundation
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