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

Front Biosci (Landmark Ed). 2022 Aug 16;27(8):245. doi: 10.31083/j.fbl2708245.


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: MG-132; cisplatin resistance; testicular germ-cell tumor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Antineoplastic Agents* / pharmacology
  • Cell Line, Tumor
  • Cisplatin / pharmacology
  • Cisplatin / therapeutic use
  • Drug Resistance, Neoplasm / genetics
  • Humans
  • Male
  • Neoplasms, Germ Cell and Embryonal* / drug therapy
  • Neoplasms, Germ Cell and Embryonal* / genetics
  • Testicular Neoplasms


  • Antineoplastic Agents
  • Cisplatin

Supplementary concepts

  • Testicular Germ Cell Tumor