Cargando…

Tyrphostin AG 1024 modulates radiosensitivity in human breast cancer cells

Insulin-like growth factor-1 (IGF-1) plays an important growth-promoting effect by activating the PI3K/Akt signalling pathway, inhibiting apoptotic pathways and mediating mitogenic actions. Tyrphostin AG 1024, one selective inhibitor of IGF-1R, was used to evaluate effects on proliferation, radiosen...

Descripción completa

Detalles Bibliográficos
Autores principales: Wen, B, Deutsch, E, Marangoni, E, Frascona, V, Maggiorella, L, Abdulkarim, B, Chavaudra, N, Bourhis, J
Formato: Texto
Lenguaje:English
Publicado: Nature Publishing Group 2001
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2364012/
https://www.ncbi.nlm.nih.gov/pubmed/11747348
http://dx.doi.org/10.1054/bjoc.2001.2171
_version_ 1782153848004018176
author Wen, B
Deutsch, E
Marangoni, E
Frascona, V
Maggiorella, L
Abdulkarim, B
Chavaudra, N
Bourhis, J
author_facet Wen, B
Deutsch, E
Marangoni, E
Frascona, V
Maggiorella, L
Abdulkarim, B
Chavaudra, N
Bourhis, J
author_sort Wen, B
collection PubMed
description Insulin-like growth factor-1 (IGF-1) plays an important growth-promoting effect by activating the PI3K/Akt signalling pathway, inhibiting apoptotic pathways and mediating mitogenic actions. Tyrphostin AG 1024, one selective inhibitor of IGF-1R, was used to evaluate effects on proliferation, radiosensitivity, and radiation-induced cell apoptosis in a human breast cancer cell line MCF-7. Exposure to Tyrphostin AG 1024 inhibited proliferation and induced apoptosis in a time-dependent manner, and the degree of growth inhibition for IC20 plus irradiation (4 Gy) was up to 50% compared to the control. Examination of Tyrphostin AG 1024 effects on radiation response demonstrated a marked enhancement in radiosensitivity and amplification of radiation-induced apoptosis. Western blot analysis indicated that Tyrphostin AG 1024-induced apoptosis was associated with a downregulation of expression of phospho-Akt1, increased expression of Bax, p53 and p21, and a decreased expression of bcl-2 expression, especially when combined with irradiation. To our knowledge, this is the first report showing that an IGF-1 inhibitor was able to markedly increase the response of tumour cells to ionizing radiation. These results suggest that Tyrphostin AG 1024 could be used as a potential therapeutic agent in combination with irradiation.   http://www.bjcancer.com © 2001 Cancer Research Campaign
format Text
id pubmed-2364012
institution National Center for Biotechnology Information
language English
publishDate 2001
publisher Nature Publishing Group
record_format MEDLINE/PubMed
spelling pubmed-23640122009-09-10 Tyrphostin AG 1024 modulates radiosensitivity in human breast cancer cells Wen, B Deutsch, E Marangoni, E Frascona, V Maggiorella, L Abdulkarim, B Chavaudra, N Bourhis, J Br J Cancer Regular Article Insulin-like growth factor-1 (IGF-1) plays an important growth-promoting effect by activating the PI3K/Akt signalling pathway, inhibiting apoptotic pathways and mediating mitogenic actions. Tyrphostin AG 1024, one selective inhibitor of IGF-1R, was used to evaluate effects on proliferation, radiosensitivity, and radiation-induced cell apoptosis in a human breast cancer cell line MCF-7. Exposure to Tyrphostin AG 1024 inhibited proliferation and induced apoptosis in a time-dependent manner, and the degree of growth inhibition for IC20 plus irradiation (4 Gy) was up to 50% compared to the control. Examination of Tyrphostin AG 1024 effects on radiation response demonstrated a marked enhancement in radiosensitivity and amplification of radiation-induced apoptosis. Western blot analysis indicated that Tyrphostin AG 1024-induced apoptosis was associated with a downregulation of expression of phospho-Akt1, increased expression of Bax, p53 and p21, and a decreased expression of bcl-2 expression, especially when combined with irradiation. To our knowledge, this is the first report showing that an IGF-1 inhibitor was able to markedly increase the response of tumour cells to ionizing radiation. These results suggest that Tyrphostin AG 1024 could be used as a potential therapeutic agent in combination with irradiation.   http://www.bjcancer.com © 2001 Cancer Research Campaign Nature Publishing Group 2001-12 /pmc/articles/PMC2364012/ /pubmed/11747348 http://dx.doi.org/10.1054/bjoc.2001.2171 Text en Copyright © 2001 Cancer Research Campaign https://creativecommons.org/licenses/by/4.0/This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material.If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/.
spellingShingle Regular Article
Wen, B
Deutsch, E
Marangoni, E
Frascona, V
Maggiorella, L
Abdulkarim, B
Chavaudra, N
Bourhis, J
Tyrphostin AG 1024 modulates radiosensitivity in human breast cancer cells
title Tyrphostin AG 1024 modulates radiosensitivity in human breast cancer cells
title_full Tyrphostin AG 1024 modulates radiosensitivity in human breast cancer cells
title_fullStr Tyrphostin AG 1024 modulates radiosensitivity in human breast cancer cells
title_full_unstemmed Tyrphostin AG 1024 modulates radiosensitivity in human breast cancer cells
title_short Tyrphostin AG 1024 modulates radiosensitivity in human breast cancer cells
title_sort tyrphostin ag 1024 modulates radiosensitivity in human breast cancer cells
topic Regular Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2364012/
https://www.ncbi.nlm.nih.gov/pubmed/11747348
http://dx.doi.org/10.1054/bjoc.2001.2171
work_keys_str_mv AT wenb tyrphostinag1024modulatesradiosensitivityinhumanbreastcancercells
AT deutsche tyrphostinag1024modulatesradiosensitivityinhumanbreastcancercells
AT marangonie tyrphostinag1024modulatesradiosensitivityinhumanbreastcancercells
AT frasconav tyrphostinag1024modulatesradiosensitivityinhumanbreastcancercells
AT maggiorellal tyrphostinag1024modulatesradiosensitivityinhumanbreastcancercells
AT abdulkarimb tyrphostinag1024modulatesradiosensitivityinhumanbreastcancercells
AT chavaudran tyrphostinag1024modulatesradiosensitivityinhumanbreastcancercells
AT bourhisj tyrphostinag1024modulatesradiosensitivityinhumanbreastcancercells