title: Inhibition of polo-like kinase 1 induces cell cycle arrest and sensitizes glioblastoma cells to ionizing radiation.
abstract: Despite efforts to improve surgical, radiologic, and chemotherapeutic strategies, the outcome of patients with glioblastoma (GBM) is still poor. Polo-like kinase 1 (PLK1) is a serine/threonine kinase that plays key roles in cell cycle control and has been associated with tumor growth and prognosis. Here, we aimed at testing the radiosensitizing effects of the PLK1 inhibitor BI 2536 on eight GBM cell lines. For cell cycle analysis, T98G, U251, U343 MG-a, LN319, SF188, U138 MG, and U87 MG cell lines were treated with 10, 50, or 100 nM of BI 2536 for 24 hours. In addition, cell cultures exposed to BI 2536 50 nM for 24 hours were irradiated with γ-rays from (60)Cobalt source at final doses of 2, 4, and 6 Gy. Combinatorial effects were evaluated through proliferation and clonogenic capacity assays. Treatment with BI 2536 caused mitotic arrest after 24 hours, and increased apoptosis in GBM cells. Moreover, our results demonstrate that pretreatment with this drug sensitized six out of seven GBM cell lines to different doses of γ-irradiation as shown by decreased growth and abrogation of colony-formation capacity. Our data suggest that PLK1 blockage has a radiosensitizing effect on GBM, which could improve treatment strategies for this devastating tumor.
authors.affiliation: Department of Genetics, University of São Paulo, Brazil. julia.pezuk@hotmail.com
authors.forename: Julia Alejandra
authors.initials: JA
authors.lastname: Pezuk
authors.forename: María Sol
authors.initials: MS
authors.lastname: Brassesco
authors.forename: Andressa Gois
authors.initials: AG
authors.lastname: Morales
authors.forename: Jaqueline Carvalho
authors.initials: JC
authors.lastname: de Oliveira
authors.forename: Harley Francisco
authors.initials: HF
authors.lastname: de Oliveira
authors.forename: Carlos Alberto
authors.initials: CA
authors.lastname: Scrideli
authors.forename: Luiz Gonzaga
authors.initials: LG
authors.lastname: Tone
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D059447:Cell Cycle Checkpoints / Q000187:drug effects / Q000528:radiation effects; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D048708:Cell Growth Processes / Q000187:drug effects / Q000528:radiation effects; D045744:Cell Line, Tumor; D005909:Glioblastoma / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology / Q000532:radiotherapy*; D006801:Humans; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011621:Pteridines / Q000494:pharmacology*; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D000097869:Polo-Like Kinase 1
chemical_list: D018797:Cell Cycle Proteins; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D011621:Pteridines; D011838:Radiation-Sensitizing Agents; D000097869:Polo-Like Kinase 1; C518477:BI 2536