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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Author(s):
Pezuk, J. A. [1] ; Brassesco, M. S. [2] ; Morales, A. G. [1] ; de Oliveira, J. C. [1] ; de Paula Queiroz, R. G. [2] ; Machado, H. R. [3] ; Carlotti, Jr., C. G. [3] ; Neder, L. [4] ; Scrideli, C. A. ; Tone, L. G. [2]
Total Authors: 10
Affiliation:
[1] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Genet, BR-05508 Sao Paulo - Brazil
[2] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Pediat, BR-05508 Sao Paulo - Brazil
[3] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Surg & Anat, BR-05508 Sao Paulo - Brazil
[4] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Pathol, BR-05508 Sao Paulo - Brazil
Total Affiliations: 4
Document type: Journal article
Source: Cancer Gene Therapy; v. 20, n. 9, p. 499-506, SEP 2013.
Web of Science Citations: 29
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. (AU)

FAPESP's process: 09/11053-2 - Evaluation of Polo-like kinases genes expression in glioblastoma cell lines and samples
Grantee:Julia Alejandra Pezuk
Support type: Scholarships in Brazil - Master