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DOI: 10.1055/s-0030-1254472
Plk1 is a novel target for high-risk neuroblastoma therapy
Aims: To determine Plk1 as a potential target for neuroblastoma therapy.
Methods: PLK1 transcript levels of 476 neuroblastomas were correlated with prognostic markers and outcome. Seven neuroblastoma cell lines were treated with various concentrations of BI 2536 and changes in cell proliferation and cell cycle distribution were determined. Nude mice with IMR-32 neuroblastoma xenografts were treated with BI 2536.
Results: PLK1 up-regulation is associated with unfavorable markers such as stage 4, age >18 months and MYCN amplification (p<0.001 each), as well as unfavorable gene expression-based classification and adverse patient outcome (p<0.001 each). Plk1 was strongly expressed at the protein level in neuroblastoma cell lines and in samples from patients with poor outcome. On treatment with nanomolar doses of BI 2536, all seven neuroblastoma cell lines showed reduced proliferation, cell cycle arrest and cell death with LC50 values ranging from 2.2 nmol/L to 31.2 nmol/L. BI 2536 treatment of nude mice bearing IMR-32 neuroblastoma xenografts resulted in significant inhibition of tumor growth (p<0.001).
Conclusions: Plk1 is a promising target for high-risk neuroblastoma treatment.
Keywords: BI 2536; PLK1; Kinase Inhibitor; Disease Progression; Therapy