{Reference Type}: Journal Article
{Title}: The CDK Inhibitor Dinaciclib Improves Cisplatin Response in Nonseminomatous Testicular Cancer: A Preclinical Study.
{Author}: Rossini E;Tamburello M;Abate A;Zini S;Ribaudo G;Gianoncelli A;Calza S;Valcamonico F;Suardi NR;Mirabella G;Berruti A;Sigala S;
{Journal}: Cells
{Volume}: 13
{Issue}: 5
{Year}: 2024 Feb 20
{Factor}: 7.666
{DOI}: 10.3390/cells13050368
{Abstract}: <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.