The involvement of FOXO1 in cytotoxic stress and drug-resistance induced by paclitaxel in ovarian cancers

The role of transcriptional factor FOXO1 in the mechanism of drug-resistance in ovarian cancer has not been elucidated. In ovarian cancer cell lines, FOXO1 expression and its correlation with paclitaxel treatment was investigated by cytotoxic assay and silencing experiment. Clinical ovarian cancer s...

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Autores principales: Goto, T, Takano, M, Hirata, J, Tsuda, H
Formato: Texto
Lenguaje:English
Publicado: Nature Publishing Group 2008
Materias:
Translational Therapeutics
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2275483/
https://www.ncbi.nlm.nih.gov/pubmed/18319717
http://dx.doi.org/10.1038/sj.bjc.6604279
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author Goto, T
Takano, M
Hirata, J
Tsuda, H
author_facet Goto, T
Takano, M
Hirata, J
Tsuda, H
author_sort Goto, T
collection PubMed
description The role of transcriptional factor FOXO1 in the mechanism of drug-resistance in ovarian cancer has not been elucidated. In ovarian cancer cell lines, FOXO1 expression and its correlation with paclitaxel treatment was investigated by cytotoxic assay and silencing experiment. Clinical ovarian cancer samples were also examined for FOXO1 expression by immunohistochemistry. FOXO1 expression was distinctively upregulated in paclitaxel-resistant cell line, and enhanced by exposure to paclitaxel. FOXO1 overexpression was frequently observed in tissue samples from chemoresistant patients compared to chemosensitive patients. FOXO1 silencing in paclitaxel-resistant cell line decreased its resistance. Modification of oxidative stress by co-treatment with pharmacologic modulators of reactive oxygen species attenuated cytotoxicity of paclitaxel. Downstream targets of FOXO1 involving oxidative stress were also attenuated in silencing experiment, suggesting its involvement in altered sensitivity to paclitaxel. These results indicate that FOXO1 links to cytotoxic stress induced by paclitaxel and contributes to the drug-resistance in ovarian cancers.
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spelling pubmed-22754832009-09-10 The involvement of FOXO1 in cytotoxic stress and drug-resistance induced by paclitaxel in ovarian cancers Goto, T Takano, M Hirata, J Tsuda, H Br J Cancer Translational Therapeutics The role of transcriptional factor FOXO1 in the mechanism of drug-resistance in ovarian cancer has not been elucidated. In ovarian cancer cell lines, FOXO1 expression and its correlation with paclitaxel treatment was investigated by cytotoxic assay and silencing experiment. Clinical ovarian cancer samples were also examined for FOXO1 expression by immunohistochemistry. FOXO1 expression was distinctively upregulated in paclitaxel-resistant cell line, and enhanced by exposure to paclitaxel. FOXO1 overexpression was frequently observed in tissue samples from chemoresistant patients compared to chemosensitive patients. FOXO1 silencing in paclitaxel-resistant cell line decreased its resistance. Modification of oxidative stress by co-treatment with pharmacologic modulators of reactive oxygen species attenuated cytotoxicity of paclitaxel. Downstream targets of FOXO1 involving oxidative stress were also attenuated in silencing experiment, suggesting its involvement in altered sensitivity to paclitaxel. These results indicate that FOXO1 links to cytotoxic stress induced by paclitaxel and contributes to the drug-resistance in ovarian cancers. Nature Publishing Group 2008-03-25 2008-03-04 /pmc/articles/PMC2275483/ /pubmed/18319717 http://dx.doi.org/10.1038/sj.bjc.6604279 Text en Copyright © 2008 Cancer Research UK 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 Translational Therapeutics
Goto, T
Takano, M
Hirata, J
Tsuda, H
The involvement of FOXO1 in cytotoxic stress and drug-resistance induced by paclitaxel in ovarian cancers
title The involvement of FOXO1 in cytotoxic stress and drug-resistance induced by paclitaxel in ovarian cancers
title_full The involvement of FOXO1 in cytotoxic stress and drug-resistance induced by paclitaxel in ovarian cancers
title_fullStr The involvement of FOXO1 in cytotoxic stress and drug-resistance induced by paclitaxel in ovarian cancers
title_full_unstemmed The involvement of FOXO1 in cytotoxic stress and drug-resistance induced by paclitaxel in ovarian cancers
title_short The involvement of FOXO1 in cytotoxic stress and drug-resistance induced by paclitaxel in ovarian cancers
title_sort involvement of foxo1 in cytotoxic stress and drug-resistance induced by paclitaxel in ovarian cancers
topic Translational Therapeutics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2275483/
https://www.ncbi.nlm.nih.gov/pubmed/18319717
http://dx.doi.org/10.1038/sj.bjc.6604279
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