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Polo-like kinase 1 inhibition causes decreased proliferation by cell cycle arrest, leading to cell death in glioblastoma

Cancer Gene Therapy volume 20, pages 499–506 (2013)Cite this article

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Abstract

Glioblastoma (GBM) is one of the most aggressive central nervous system tumors with a patient’s median survival of <1 year. Polo-like kinases (PLKs) are a family of serine/threonine kinases that have key roles in cell cycle control and DNA-damage response. We evaluated PLK1, 2, 3 and 4 gene expression in 8 GBM cell lines and 17 tumor samples, and analyzed the effect of the PLK1 inhibition on SF188 and T98G GBM cell lines and 13 primary cultures. Our data showed PLK1 overexpression and a variable altered expression of PLK2, 3 and 4 genes in GBM tumor samples and cell lines. Treatments with nanomolar concentrations of BI 2536, BI 6727, GW843682X or GSK461364 caused a significant decrease in GBM cells proliferation. Colony formation was also found to be inhibited (P<0.05), whereas apoptosis rate and mitotic index were significantly increased (P<0.05) after PLK1 inhibition in both GBM cell lines. Cell cycle analysis showed an arrest at G2 (P<0.05) and cell invasion was also decreased after PLK1 inhibition. Furthermore, simultaneous combinations of BI 2536 and temozolomide produced synergistic effects for both the cell lines after 48 h of treatment. Our findings suggest that PLK1 might be a promising target for the treatment of GBMs.

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Acknowledgements

We are grateful to Dr Elza Tiemi Sakamoto-Hojo and Ana Paula de Lima Montaldi (MSc) for facilitating cell cycle analysis, to Kleiton Borges Silva (MSc) for helping with the primary tumor cultures expansion, and to Veridiana Kiill Suazo (BSc) for technical assistance. We also thank the Foundation for Research Support of São Paulo (FAPESP # 2009/50118-2 and 2009/11053-2) and the Coordination of Improvement of Higher Education Personnel (CAPES) for financial support.

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Authors and Affiliations

  1. Department of Genetics, Faculty of Medicine of Ribeirão Preto, University of São Paulo,

    J A Pezuk, A G Morales & J C de Oliveira

  2. Department of Pediatrics, Faculty of Medicine of Ribeirão Preto, University of São Paulo,

    M S Brassesco, R G de Paula Queiroz, C A Scrideli & L G Tone

  3. Department of Surgery and Anatomy, Faculty of Medicine of Ribeirão Preto, University of São Paulo,

    H R Machado & C G Carlotti Jr

  4. Department of Pathology, Faculty of Medicine of Ribeirão Preto, University of São Paulo,

    L Neder

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  1. J A Pezuk
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Correspondence to J A Pezuk.

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Pezuk, J., Brassesco, M., Morales, A. et al. Polo-like kinase 1 inhibition causes decreased proliferation by cell cycle arrest, leading to cell death in glioblastoma. Cancer Gene Ther 20, 499–506 (2013). https://doi.org/10.1038/cgt.2013.46

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