PUBLICATION
The CDK Inhibitor Dinaciclib Improves Cisplatin Response in Nonseminomatous Testicular Cancer: A Preclinical Study
- Authors
- Rossini, E., Tamburello, M., Abate, A., Zini, S., Ribaudo, G., Gianoncelli, A., Calza, S., Valcamonico, F., Suardi, N.R., Mirabella, G., Berruti, A., Sigala, S.
- ID
- ZDB-PUB-240313-14
- Date
- 2024
- Source
- Cells 13(5): (Journal)
- Registered Authors
- Keywords
- CDK inhibitors, cisplatin resistance, combined treatment, dinaciclib, testicular cancer, zebrafish xenograft
- MeSH Terms
-
- Indolizines*
- Cell Proliferation
- Testicular Neoplasms*
- Neoplasms, Germ Cell and Embryonal*
- Zebrafish
- Protein Kinase Inhibitors/pharmacology
- Male
- Pyridinium Compounds*
- Animals
- Humans
- Cisplatin*/pharmacology
- Cyclic N-Oxides*
- PubMed
- 38474332 Full text @ Cells
Citation
Rossini, E., Tamburello, M., Abate, A., Zini, S., Ribaudo, G., Gianoncelli, A., Calza, S., Valcamonico, F., Suardi, N.R., Mirabella, G., Berruti, A., Sigala, S. (2024) The CDK Inhibitor Dinaciclib Improves Cisplatin Response in Nonseminomatous Testicular Cancer: A Preclinical Study. Cells. 13(5):.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping