Inhibition of Polo-Like Kinase 1 Induces Cell Cycle Arrest and Sensitizes Glioblastoma Cells to Ionizing Radiation

Pezuk, Julia Alejandra; Brassesco, María Sol; Morales, Andressa Gois; Oliveira, Jaqueline Carvalho de; Oliveira, Harley Francisco de; Scrideli, Carlos Alberto; Tone, Luíz Gonzaga

doi:10.1089/cbr.2012.1415

Cited by 26 publications

(21 citation statements)

References 43 publications

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“…In line with our findings, several other studies reported that the combination of Plk1 inhibition with radiotherapy leads to synergistic cell killing in vitro in multiple cancer types such as breast cancer, NSCLC, cervical epithelial adenocarcinoma, medulloblastoma, osteocarcinoma, glioblastoma, Merkel cell carcinoma, colorectal cancer, bladder carcinoma, oral cancer, and esophageal squamous cell carcinoma [8,[28][29][30][31][32][33][34][35][36][37][38][39][40]. In vivo, Dong et al demonstrated a synergistic inhibition of tumor growth and prolonged median survival in a tumor xenograft murine model with glioblastoma stem cells after treatment with volasertib and radiation [38].…”

Section: Discussionsupporting

confidence: 92%

Radiosensitization of Non-Small Cell Lung Cancer Cells by the Plk1 Inhibitor Volasertib Is Dependent on the p53 Status

Bossche

Domen

Peeters

et al. 2019

Cancers

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Polo-like kinase 1 (Plk1), a master regulator of mitotic cell division, is highly expressed in non-small cell lung cancer (NSCLC) making it an interesting drug target. We examined the in vitro therapeutic effects of volasertib, a Plk1 inhibitor, in combination with irradiation in a panel of NSCLC cell lines with different p53 backgrounds. Pretreatment with volasertib efficiently sensitized p53 wild type cells to irradiation. Flow cytometric analysis revealed that significantly more cells were arrested in the G2/M phase of the cell cycle after the combination therapy compared to either treatment alone (p < 0.005). No significant synergistic induction of apoptotic cell death was observed, but, importantly, significantly more senescent cells were detected when cells were pretreated with volasertib before irradiation compared to both monotherapies alone (p < 0.001), especially in cells with functional p53. Consequently, while most cells with functional p53 showed permanent growth arrest, more p53 knockdown/mutant cells could re-enter the cell cycle, resulting in colony formation and cell survival. Our findings assign functional p53 as a determining factor for the observed radiosensitizing effect of volasertib in combination with radiotherapy for the treatment of NSCLC.

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Section: Discussionsupporting

confidence: 92%

Radiosensitization of Non-Small Cell Lung Cancer Cells by the Plk1 Inhibitor Volasertib Is Dependent on the p53 Status

Bossche

Domen

Peeters

et al. 2019

Cancers

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“…PLK1 knockdown has been shown to enhance radiation efficacy in prostate and rectal cancer [39,40], head-and-neck squamous cell carcinoma [41], and medulloblastoma [42]. Its pharmacological inhibition by BI 2536 has also shown similar results [43,44]. Exposure of different GBM cells to GSK461364 before radiation has also resulted in an increase in their radiosensitivity, with DERs ranging from 1.40 to 1.53 [45].…”

Section: Discussionmentioning

confidence: 99%

BI 6727 and GSK461364 suppress growth and radiosensitize osteosarcoma cells, but show limited cytotoxic effects when combined with conventional treatments

Bogado

Pezuk²,

Oliveira³

et al. 2015

Anti-Cancer Drugs

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Polo-like kinase 1 (PLK1), a key regulator of mitosis, is often overexpressed in childhood cancers and is associated with poor prognosis. Previous reports have shown that inhibition of PLK1 might serve as a promising anticancer treatment for osteosarcoma. In this study, we tested the second-generation PLK1 inhibitors BI 6727 and GSK461364 in HOS and MG-63 cell lines, both as a single agent and in combination with methotrexate, cisplatin, vinblastine, doxorubicin, or ionizing radiation. Both PLK1 inhibitors worked equally in terms of cell growth arrest, apoptosis induction, and radiosensitization. Combining BI 6727 or GSK461364 with conventional treatments, however, showed trivial synergistic antitumor effects in vitro. Our results reinforce the potential use of PLK1 inhibitors for a pharmacologic intervention in osteosarcoma, although their applicability in polychemotherapeutic regimens deserves further investigation.

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“…(the SFs were between 33.6% and 69.7%) [16]. Thus, BI6727 at 50 nM was used in the combinatory chemo-irradiation treatment throughout.…”

Section: Discussionmentioning

confidence: 99%

Polo-like kinase 1 inhibitor BI6727 sensitizes 9L gliosarcoma cells to ionizing irradiation

Engels

Davis

et al. 2019

Biomed. Phys. Eng. Express

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Inhibition of Polo-Like Kinase 1 Induces Cell Cycle Arrest and Sensitizes Glioblastoma Cells to Ionizing Radiation

Cited by 26 publications

References 43 publications

Radiosensitization of Non-Small Cell Lung Cancer Cells by the Plk1 Inhibitor Volasertib Is Dependent on the p53 Status

Radiosensitization of Non-Small Cell Lung Cancer Cells by the Plk1 Inhibitor Volasertib Is Dependent on the p53 Status

BI 6727 and GSK461364 suppress growth and radiosensitize osteosarcoma cells, but show limited cytotoxic effects when combined with conventional treatments

Polo-like kinase 1 inhibitor BI6727 sensitizes 9L gliosarcoma cells to ionizing irradiation

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