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BMC Cancer
Published in: BMC Cancer 1/2016

Open Access 01-12-2016 | Research article

Polo-like Kinase 1 as a potential therapeutic target in Diffuse Intrinsic Pontine Glioma

Authors: Vladimir Amani, Eric W Prince, Irina Alimova, Ilango Balakrishnan, Diane Birks, Andrew M. Donson, Peter Harris, Jean M. Mulcahy Levy, Michael Handler, Nicholas K. Foreman, Sujatha Venkataraman, Rajeev Vibhakar

Published in: BMC Cancer | Issue 1/2016

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Abstract

Background

Diffuse intrinsic pontine gliomas (DIPGs) are highly aggressive, fatal, childhood tumors that arise in the brainstem. DIPGs have no effective treatment, and their location and diffuse nature render them inoperable. Radiation therapy remains the only standard of care for this devastating disease. New therapeutic targets are needed to develop novel therapy for DIPG.

Methods

We examined the expression of PLK1 mRNA in DIPG tumor samples through microarray analysis and found it to be up regulated versus normal pons. Using the DIPG tumor cells, we inhibited PLK1 using a clinically relevant specific inhibitor BI 6727 and evaluated the effects on, proliferation, apoptosis, induction of DNA damage and radio sensitization of the DIPG tumor cells.

Results

Treatment of DIPG cell lines with BI 6727, a new generation, highly selective inhibitor of PLK1, resulted in decreased cell proliferation and a marked increase in cellular apoptosis. Cell cycle analysis showed a significant arrest in G2-M phase and a substantial increase in cell death. Treatment also resulted in an increased γH2AX expression, indicating induction of DNA damage. PLK1 inhibition resulted in radiosensitization of DIPG cells.

Conclusion

These findings suggest that targeting PLK1 with small-molecule inhibitors, in combination with radiation therapy, will hold a novel strategy in the treatment of DIPG that warrants further investigation.
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Metadata
Title
Polo-like Kinase 1 as a potential therapeutic target in Diffuse Intrinsic Pontine Glioma
Authors
Vladimir Amani
Eric W Prince
Irina Alimova
Ilango Balakrishnan
Diane Birks
Andrew M. Donson
Peter Harris
Jean M. Mulcahy Levy
Michael Handler
Nicholas K. Foreman
Sujatha Venkataraman
Rajeev Vibhakar
Publication date
01-12-2016
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2016
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-016-2690-6

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