The CDK Inhibitor Dinaciclib Improves Cisplatin Response in Nonseminomatous Testicular Cancer: A Preclinical Study.
Cells
; 13(5)2024 Feb 20.
Article
in En
| MEDLINE
| ID: mdl-38474332
ABSTRACT
BACKGROUND:
Most patients with testicular germ cell tumors (GCTs) are treated with cisplatin (CP)-based chemotherapy. However, some of them may develop CP resistance and therefore represent a clinical challenge. Cyclin-dependent kinase 5 (CDK5) is involved in chemotherapy resistance in different types of cancer. Here, we investigated the possible role of CDK5 and other CDKs targeted by dinaciclib in nonseminoma cell models (both CP-sensitive and CP-resistant), evaluating the potential of the CDK inhibitor dinaciclib as a single/combined agent for the treatment of advanced/metastatic testicular cancer (TC).METHODS:
The effects of dinaciclib and CP on sensitive and resistant NT2/D1 and NCCIT cell viability and proliferation were evaluated using MTT assays and direct count methods. Flow cytometry cell-cycle analysis was performed. The protein expression was assessed via Western blotting. The in vivo experiments were conducted in zebrafish embryos xenografted with TC cells.RESULTS:
Among all the CDKs analyzed, CDK5 protein expression was significantly higher in CP-resistant models. Dinaciclib reduced the cell viability and proliferation in each cell model, inducing changes in cell-cycle distribution. In drug combination experiments, dinaciclib enhances the CP effect both in vitro and in the zebrafish model.CONCLUSIONS:
Dinaciclib, when combined with CP, could be useful for improving nonseminoma TC response to CP.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Pyridinium Compounds
/
Testicular Neoplasms
/
Cisplatin
/
Neoplasms, Germ Cell and Embryonal
/
Cyclic N-Oxides
/
Indolizines
Limits:
Animals
/
Humans
/
Male
Language:
En
Journal:
Cells
Year:
2024
Type:
Article
Affiliation country:
Italy