Idarubicin combats abiraterone and enzalutamide resistance in prostate cells via targeting XPA protein

Although second-generation therapies like abiraterone (ABI) and enzalutamide (ENZ) benefit patients with castration-resistant prostate cancer (CRPC), drug resistance frequently occurs, eventually resulting in therapy failure. In this study, we used two libraries, FDA-approved drug library and CRISP/...

Descripción completa

Detalles Bibliográficos
Autores principales: Zhang, Ying, Wei, Wei, Li, Changying, Yan, Siyuan, Wang, Shanshan, Xiao, Shudong, He, Chenchen, Li, Jing, Qi, Zhi, Li, Benyi, Yang, Kuo, Li, Changlin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9744908/
https://www.ncbi.nlm.nih.gov/pubmed/36509750
http://dx.doi.org/10.1038/s41419-022-05490-5
_version_ 1784849031431716864
author Zhang, Ying
Wei, Wei
Li, Changying
Yan, Siyuan
Wang, Shanshan
Xiao, Shudong
He, Chenchen
Li, Jing
Qi, Zhi
Li, Benyi
Yang, Kuo
Li, Changlin
author_facet Zhang, Ying
Wei, Wei
Li, Changying
Yan, Siyuan
Wang, Shanshan
Xiao, Shudong
He, Chenchen
Li, Jing
Qi, Zhi
Li, Benyi
Yang, Kuo
Li, Changlin
author_sort Zhang, Ying
collection PubMed
description Although second-generation therapies like abiraterone (ABI) and enzalutamide (ENZ) benefit patients with castration-resistant prostate cancer (CRPC), drug resistance frequently occurs, eventually resulting in therapy failure. In this study, we used two libraries, FDA-approved drug library and CRISP/Cas9 knockout (GeCKO) library to screen for drugs that overcome treatment resistance and to identify the potential drug-resistant genes involved in treatment resistance. Our screening results showed that the DNA-damaging agent idarubicin (IDA) overcame abiraterone and enzalutamide resistance in prostate cancer cells. IDA treatment inhibited the DNA repair protein XPA expression in a transcription-independent manner. Consistently, XPA knockout sensitized prostate cancer cells to abiraterone and enzalutamide treatment. In conclusion, IDA combats abiraterone and enzalutamide resistance by reducing XPA protein level in prostate cancer.
format Online
Article
Text
id pubmed-9744908
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-97449082022-12-14 Idarubicin combats abiraterone and enzalutamide resistance in prostate cells via targeting XPA protein Zhang, Ying Wei, Wei Li, Changying Yan, Siyuan Wang, Shanshan Xiao, Shudong He, Chenchen Li, Jing Qi, Zhi Li, Benyi Yang, Kuo Li, Changlin Cell Death Dis Article Although second-generation therapies like abiraterone (ABI) and enzalutamide (ENZ) benefit patients with castration-resistant prostate cancer (CRPC), drug resistance frequently occurs, eventually resulting in therapy failure. In this study, we used two libraries, FDA-approved drug library and CRISP/Cas9 knockout (GeCKO) library to screen for drugs that overcome treatment resistance and to identify the potential drug-resistant genes involved in treatment resistance. Our screening results showed that the DNA-damaging agent idarubicin (IDA) overcame abiraterone and enzalutamide resistance in prostate cancer cells. IDA treatment inhibited the DNA repair protein XPA expression in a transcription-independent manner. Consistently, XPA knockout sensitized prostate cancer cells to abiraterone and enzalutamide treatment. In conclusion, IDA combats abiraterone and enzalutamide resistance by reducing XPA protein level in prostate cancer. Nature Publishing Group UK 2022-12-12 /pmc/articles/PMC9744908/ /pubmed/36509750 http://dx.doi.org/10.1038/s41419-022-05490-5 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access 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 http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Zhang, Ying
Wei, Wei
Li, Changying
Yan, Siyuan
Wang, Shanshan
Xiao, Shudong
He, Chenchen
Li, Jing
Qi, Zhi
Li, Benyi
Yang, Kuo
Li, Changlin
Idarubicin combats abiraterone and enzalutamide resistance in prostate cells via targeting XPA protein
title Idarubicin combats abiraterone and enzalutamide resistance in prostate cells via targeting XPA protein
title_full Idarubicin combats abiraterone and enzalutamide resistance in prostate cells via targeting XPA protein
title_fullStr Idarubicin combats abiraterone and enzalutamide resistance in prostate cells via targeting XPA protein
title_full_unstemmed Idarubicin combats abiraterone and enzalutamide resistance in prostate cells via targeting XPA protein
title_short Idarubicin combats abiraterone and enzalutamide resistance in prostate cells via targeting XPA protein
title_sort idarubicin combats abiraterone and enzalutamide resistance in prostate cells via targeting xpa protein
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9744908/
https://www.ncbi.nlm.nih.gov/pubmed/36509750
http://dx.doi.org/10.1038/s41419-022-05490-5
work_keys_str_mv AT zhangying idarubicincombatsabirateroneandenzalutamideresistanceinprostatecellsviatargetingxpaprotein
AT weiwei idarubicincombatsabirateroneandenzalutamideresistanceinprostatecellsviatargetingxpaprotein
AT lichangying idarubicincombatsabirateroneandenzalutamideresistanceinprostatecellsviatargetingxpaprotein
AT yansiyuan idarubicincombatsabirateroneandenzalutamideresistanceinprostatecellsviatargetingxpaprotein
AT wangshanshan idarubicincombatsabirateroneandenzalutamideresistanceinprostatecellsviatargetingxpaprotein
AT xiaoshudong idarubicincombatsabirateroneandenzalutamideresistanceinprostatecellsviatargetingxpaprotein
AT hechenchen idarubicincombatsabirateroneandenzalutamideresistanceinprostatecellsviatargetingxpaprotein
AT lijing idarubicincombatsabirateroneandenzalutamideresistanceinprostatecellsviatargetingxpaprotein
AT qizhi idarubicincombatsabirateroneandenzalutamideresistanceinprostatecellsviatargetingxpaprotein
AT libenyi idarubicincombatsabirateroneandenzalutamideresistanceinprostatecellsviatargetingxpaprotein
AT yangkuo idarubicincombatsabirateroneandenzalutamideresistanceinprostatecellsviatargetingxpaprotein
AT lichanglin idarubicincombatsabirateroneandenzalutamideresistanceinprostatecellsviatargetingxpaprotein

Ejemplares similares