Radioresistance of human glioma spheroids and expression of HSP70, p53 and EGFr
Autor(a) principal: | |
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Data de Publicação: | 2011 |
Outros Autores: | , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UFRGS |
Texto Completo: | http://hdl.handle.net/10183/111830 |
Resumo: | Background: Radiation therapy is routinely prescribed for high-grade malignant gliomas. However, the efficacy of this therapeutic modality is often limited by the occurrence of radioresistance, reflected as a diminished susceptibility of the irradiated cells to undergo cell death. Thus, cells have evolved an elegant system in response to ionizing radiation induced DNA damage, where p53, Hsp70 and/or EGFr may play an important role in the process. In the present study, we investigated whether the content of p53, Hsp70 and EGFr are associated to glioblastoma (GBM) cell radioresistance. Methods: Spheroids from U-87MG and MO59J cell lines as well as spheroids derived from primary culture of tumor tissue of one GBM patient (UGBM1) were irradiated (5, 10 and 20 Gy), their relative radioresistance were established and the p53, Hsp70 and EGFr contents were immunohistochemically determined. Moreover, we investigated whether EGFr-phospho-Akt and EGFr-MEK-ERK pathways can induce GBM radioresistance using inhibitors of activation of ERK (PD098059) and Akt (wortmannin). Results: At 5 Gy irradiation UGBM1 and U-87MG spheroids showed growth inhibition whereas the MO59J spheroid was relatively radioresistant. Overall, no significant changes in p53 and Hsp70 expression were found following 5 Gy irradiation treatment in all spheroids studied. The only difference observed in Hsp70 content was the periphery distribution in MO59J spheroids. However, 5 Gy treatment induced a significant increase on the EGFr levels in MO59J spheroids. Furthermore, treatment with inhibitors of activation of ERK (PD098059) and Akt (wortmannin) leads to radiosensitization of MO59J spheroids. Conclusions: These results indicate that the PI3K-Akt and MEK-ERK pathways triggered by EGFr confer GBM radioresistance. |
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Fedrigo, Carlos AlexandreGrivicich, IvanaSchunemann, Daniel PrettoChemale, Ivan de MelloFerreira, Daiane Nicoli Silvello dos SantosJacovas, ThaisBoschetti, Patryck StanglJotz, Geraldo PereiraBraga Filho, AroldoRocha, Adriana Brondani da2015-03-07T01:57:11Z20111748-717Xhttp://hdl.handle.net/10183/111830000953426Background: Radiation therapy is routinely prescribed for high-grade malignant gliomas. However, the efficacy of this therapeutic modality is often limited by the occurrence of radioresistance, reflected as a diminished susceptibility of the irradiated cells to undergo cell death. Thus, cells have evolved an elegant system in response to ionizing radiation induced DNA damage, where p53, Hsp70 and/or EGFr may play an important role in the process. In the present study, we investigated whether the content of p53, Hsp70 and EGFr are associated to glioblastoma (GBM) cell radioresistance. Methods: Spheroids from U-87MG and MO59J cell lines as well as spheroids derived from primary culture of tumor tissue of one GBM patient (UGBM1) were irradiated (5, 10 and 20 Gy), their relative radioresistance were established and the p53, Hsp70 and EGFr contents were immunohistochemically determined. Moreover, we investigated whether EGFr-phospho-Akt and EGFr-MEK-ERK pathways can induce GBM radioresistance using inhibitors of activation of ERK (PD098059) and Akt (wortmannin). Results: At 5 Gy irradiation UGBM1 and U-87MG spheroids showed growth inhibition whereas the MO59J spheroid was relatively radioresistant. Overall, no significant changes in p53 and Hsp70 expression were found following 5 Gy irradiation treatment in all spheroids studied. The only difference observed in Hsp70 content was the periphery distribution in MO59J spheroids. However, 5 Gy treatment induced a significant increase on the EGFr levels in MO59J spheroids. Furthermore, treatment with inhibitors of activation of ERK (PD098059) and Akt (wortmannin) leads to radiosensitization of MO59J spheroids. Conclusions: These results indicate that the PI3K-Akt and MEK-ERK pathways triggered by EGFr confer GBM radioresistance.application/pdfengRadiation oncology. London. Vol. 6 (11 Nov. 2011), p. 156 [10] f.GlioblastomaProteínas de choque térmico HSP70Proteína supressora de tumor p53Esferoides celularesRadioterapiaGlioblastomaSpheroidsRadioresistanceHsp70P53Radioresistance of human glioma spheroids and expression of HSP70, p53 and EGFrEstrangeiroinfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFRGSinstname:Universidade Federal do Rio Grande do Sul (UFRGS)instacron:UFRGSORIGINAL000953426.pdf000953426.pdfTexto completo (inglês)application/pdf557692http://www.lume.ufrgs.br/bitstream/10183/111830/1/000953426.pdf0c80b094b3937e06ed3c92fe2ac743beMD51TEXT000953426.pdf.txt000953426.pdf.txtExtracted Texttext/plain44063http://www.lume.ufrgs.br/bitstream/10183/111830/2/000953426.pdf.txt0004f2ab04a9d8ea081b995232fd3d21MD52THUMBNAIL000953426.pdf.jpg000953426.pdf.jpgGenerated Thumbnailimage/jpeg1941http://www.lume.ufrgs.br/bitstream/10183/111830/3/000953426.pdf.jpg1e2df8fc2ed39b12408cb1f7f1e35270MD5310183/1118302019-01-11 04:10:09.941513oai:www.lume.ufrgs.br:10183/111830Repositório de PublicaçõesPUBhttps://lume.ufrgs.br/oai/requestopendoar:2019-01-11T06:10:09Repositório Institucional da UFRGS - Universidade Federal do Rio Grande do Sul (UFRGS)false |
dc.title.pt_BR.fl_str_mv |
Radioresistance of human glioma spheroids and expression of HSP70, p53 and EGFr |
title |
Radioresistance of human glioma spheroids and expression of HSP70, p53 and EGFr |
spellingShingle |
Radioresistance of human glioma spheroids and expression of HSP70, p53 and EGFr Fedrigo, Carlos Alexandre Glioblastoma Proteínas de choque térmico HSP70 Proteína supressora de tumor p53 Esferoides celulares Radioterapia Glioblastoma Spheroids Radioresistance Hsp70 P53 |
title_short |
Radioresistance of human glioma spheroids and expression of HSP70, p53 and EGFr |
title_full |
Radioresistance of human glioma spheroids and expression of HSP70, p53 and EGFr |
title_fullStr |
Radioresistance of human glioma spheroids and expression of HSP70, p53 and EGFr |
title_full_unstemmed |
Radioresistance of human glioma spheroids and expression of HSP70, p53 and EGFr |
title_sort |
Radioresistance of human glioma spheroids and expression of HSP70, p53 and EGFr |
author |
Fedrigo, Carlos Alexandre |
author_facet |
Fedrigo, Carlos Alexandre Grivicich, Ivana Schunemann, Daniel Pretto Chemale, Ivan de Mello Ferreira, Daiane Nicoli Silvello dos Santos Jacovas, Thais Boschetti, Patryck Stangl Jotz, Geraldo Pereira Braga Filho, Aroldo Rocha, Adriana Brondani da |
author_role |
author |
author2 |
Grivicich, Ivana Schunemann, Daniel Pretto Chemale, Ivan de Mello Ferreira, Daiane Nicoli Silvello dos Santos Jacovas, Thais Boschetti, Patryck Stangl Jotz, Geraldo Pereira Braga Filho, Aroldo Rocha, Adriana Brondani da |
author2_role |
author author author author author author author author author |
dc.contributor.author.fl_str_mv |
Fedrigo, Carlos Alexandre Grivicich, Ivana Schunemann, Daniel Pretto Chemale, Ivan de Mello Ferreira, Daiane Nicoli Silvello dos Santos Jacovas, Thais Boschetti, Patryck Stangl Jotz, Geraldo Pereira Braga Filho, Aroldo Rocha, Adriana Brondani da |
dc.subject.por.fl_str_mv |
Glioblastoma Proteínas de choque térmico HSP70 Proteína supressora de tumor p53 Esferoides celulares Radioterapia |
topic |
Glioblastoma Proteínas de choque térmico HSP70 Proteína supressora de tumor p53 Esferoides celulares Radioterapia Glioblastoma Spheroids Radioresistance Hsp70 P53 |
dc.subject.eng.fl_str_mv |
Glioblastoma Spheroids Radioresistance Hsp70 P53 |
description |
Background: Radiation therapy is routinely prescribed for high-grade malignant gliomas. However, the efficacy of this therapeutic modality is often limited by the occurrence of radioresistance, reflected as a diminished susceptibility of the irradiated cells to undergo cell death. Thus, cells have evolved an elegant system in response to ionizing radiation induced DNA damage, where p53, Hsp70 and/or EGFr may play an important role in the process. In the present study, we investigated whether the content of p53, Hsp70 and EGFr are associated to glioblastoma (GBM) cell radioresistance. Methods: Spheroids from U-87MG and MO59J cell lines as well as spheroids derived from primary culture of tumor tissue of one GBM patient (UGBM1) were irradiated (5, 10 and 20 Gy), their relative radioresistance were established and the p53, Hsp70 and EGFr contents were immunohistochemically determined. Moreover, we investigated whether EGFr-phospho-Akt and EGFr-MEK-ERK pathways can induce GBM radioresistance using inhibitors of activation of ERK (PD098059) and Akt (wortmannin). Results: At 5 Gy irradiation UGBM1 and U-87MG spheroids showed growth inhibition whereas the MO59J spheroid was relatively radioresistant. Overall, no significant changes in p53 and Hsp70 expression were found following 5 Gy irradiation treatment in all spheroids studied. The only difference observed in Hsp70 content was the periphery distribution in MO59J spheroids. However, 5 Gy treatment induced a significant increase on the EGFr levels in MO59J spheroids. Furthermore, treatment with inhibitors of activation of ERK (PD098059) and Akt (wortmannin) leads to radiosensitization of MO59J spheroids. Conclusions: These results indicate that the PI3K-Akt and MEK-ERK pathways triggered by EGFr confer GBM radioresistance. |
publishDate |
2011 |
dc.date.issued.fl_str_mv |
2011 |
dc.date.accessioned.fl_str_mv |
2015-03-07T01:57:11Z |
dc.type.driver.fl_str_mv |
Estrangeiro info:eu-repo/semantics/article |
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info:eu-repo/semantics/publishedVersion |
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dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10183/111830 |
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1748-717X |
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000953426 |
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http://hdl.handle.net/10183/111830 |
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dc.relation.ispartof.pt_BR.fl_str_mv |
Radiation oncology. London. Vol. 6 (11 Nov. 2011), p. 156 [10] f. |
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