%0 Journal Article
%T The CDK Inhibitor Dinaciclib Improves Cisplatin Response in Nonseminomatous Testicular Cancer: A Preclinical Study.
%A Rossini E
%A Tamburello M
%A Abate A
%A Zini S
%A Ribaudo G
%A Gianoncelli A
%A Calza S
%A Valcamonico F
%A Suardi NR
%A Mirabella G
%A Berruti A
%A Sigala S
%J Cells
%V 13
%N 5
%D 2024 Feb 20
%M 38474332
%F 7.666
%R 10.3390/cells13050368
%X <B>BACKGROUND: </B>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).<BR><B>METHODS: </B>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.<BR><B>RESULTS: </B>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.<BR><B>CONCLUSIONS: </B>Dinaciclib, when combined with CP, could be useful for improving nonseminoma TC response to CP.