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Management of prostate cancer by targeting 3βHSD1 after enzalutamide and abiraterone treatment

Novel strategies for prostate cancer therapy are required to overcome resistance to abiraterone and enzalutamide. Here, we show that increasing 3βHSD1 after abiraterone and enzalutamide treatment is essential for drug resistance, and biochanin A (BCA), as an inhibitor of 3βHSD1, overcomes drug resis...

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Autores principales: Mei, Zejie, Yang, Tao, Liu, Ying, Gao, Yuanyuan, Hou, Zemin, Zhuang, Qian, He, Dongyin, Zhang, Xuebin, Tan, Qilong, Zhu, Xuyou, Qin, Yingyi, Chen, Xi, Xu, Chengdang, Bian, Cuidong, Wang, Xinan, Wang, Chenyang, Wu, Denglong, Huang, Shengsong, Li, Zhenfei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9133401/
https://www.ncbi.nlm.nih.gov/pubmed/35584629
http://dx.doi.org/10.1016/j.xcrm.2022.100608
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author Mei, Zejie
Yang, Tao
Liu, Ying
Gao, Yuanyuan
Hou, Zemin
Zhuang, Qian
He, Dongyin
Zhang, Xuebin
Tan, Qilong
Zhu, Xuyou
Qin, Yingyi
Chen, Xi
Xu, Chengdang
Bian, Cuidong
Wang, Xinan
Wang, Chenyang
Wu, Denglong
Huang, Shengsong
Li, Zhenfei
author_facet Mei, Zejie
Yang, Tao
Liu, Ying
Gao, Yuanyuan
Hou, Zemin
Zhuang, Qian
He, Dongyin
Zhang, Xuebin
Tan, Qilong
Zhu, Xuyou
Qin, Yingyi
Chen, Xi
Xu, Chengdang
Bian, Cuidong
Wang, Xinan
Wang, Chenyang
Wu, Denglong
Huang, Shengsong
Li, Zhenfei
author_sort Mei, Zejie
collection PubMed
description Novel strategies for prostate cancer therapy are required to overcome resistance to abiraterone and enzalutamide. Here, we show that increasing 3βHSD1 after abiraterone and enzalutamide treatment is essential for drug resistance, and biochanin A (BCA), as an inhibitor of 3βHSD1, overcomes drug resistance. 3βHSD1 activity increases in cell lines, biopsy samples, and patients after long-term treatment with enzalutamide or abiraterone. Enhanced steroidogenesis, mediated by 3βHSD1, is sufficient to impair enzalutamide function. In patients, accelerated abiraterone metabolism results in a decline of plasma abiraterone as disease progresses. BCA inhibits 3βHSD1 and suppresses prostate cancer development alone or together with abiraterone and enzalutamide. Daidzein, a BCA analog of dietary origin, is associated with higher plasma abiraterone concentrations and prevented prostate-specific antigen (PSA) increases in abiraterone-resistant patients. Overall, our results show that 3βHSD1 is a promising target to overcome drug resistance, and BCA suppresses disease progression as a 3βHSD1 inhibitor even after abiraterone and enzalutamide resistance.
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spelling pubmed-91334012022-05-27 Management of prostate cancer by targeting 3βHSD1 after enzalutamide and abiraterone treatment Mei, Zejie Yang, Tao Liu, Ying Gao, Yuanyuan Hou, Zemin Zhuang, Qian He, Dongyin Zhang, Xuebin Tan, Qilong Zhu, Xuyou Qin, Yingyi Chen, Xi Xu, Chengdang Bian, Cuidong Wang, Xinan Wang, Chenyang Wu, Denglong Huang, Shengsong Li, Zhenfei Cell Rep Med Article Novel strategies for prostate cancer therapy are required to overcome resistance to abiraterone and enzalutamide. Here, we show that increasing 3βHSD1 after abiraterone and enzalutamide treatment is essential for drug resistance, and biochanin A (BCA), as an inhibitor of 3βHSD1, overcomes drug resistance. 3βHSD1 activity increases in cell lines, biopsy samples, and patients after long-term treatment with enzalutamide or abiraterone. Enhanced steroidogenesis, mediated by 3βHSD1, is sufficient to impair enzalutamide function. In patients, accelerated abiraterone metabolism results in a decline of plasma abiraterone as disease progresses. BCA inhibits 3βHSD1 and suppresses prostate cancer development alone or together with abiraterone and enzalutamide. Daidzein, a BCA analog of dietary origin, is associated with higher plasma abiraterone concentrations and prevented prostate-specific antigen (PSA) increases in abiraterone-resistant patients. Overall, our results show that 3βHSD1 is a promising target to overcome drug resistance, and BCA suppresses disease progression as a 3βHSD1 inhibitor even after abiraterone and enzalutamide resistance. Elsevier 2022-04-20 /pmc/articles/PMC9133401/ /pubmed/35584629 http://dx.doi.org/10.1016/j.xcrm.2022.100608 Text en © 2022 The Author(s) https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Mei, Zejie
Yang, Tao
Liu, Ying
Gao, Yuanyuan
Hou, Zemin
Zhuang, Qian
He, Dongyin
Zhang, Xuebin
Tan, Qilong
Zhu, Xuyou
Qin, Yingyi
Chen, Xi
Xu, Chengdang
Bian, Cuidong
Wang, Xinan
Wang, Chenyang
Wu, Denglong
Huang, Shengsong
Li, Zhenfei
Management of prostate cancer by targeting 3βHSD1 after enzalutamide and abiraterone treatment
title Management of prostate cancer by targeting 3βHSD1 after enzalutamide and abiraterone treatment
title_full Management of prostate cancer by targeting 3βHSD1 after enzalutamide and abiraterone treatment
title_fullStr Management of prostate cancer by targeting 3βHSD1 after enzalutamide and abiraterone treatment
title_full_unstemmed Management of prostate cancer by targeting 3βHSD1 after enzalutamide and abiraterone treatment
title_short Management of prostate cancer by targeting 3βHSD1 after enzalutamide and abiraterone treatment
title_sort management of prostate cancer by targeting 3βhsd1 after enzalutamide and abiraterone treatment
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9133401/
https://www.ncbi.nlm.nih.gov/pubmed/35584629
http://dx.doi.org/10.1016/j.xcrm.2022.100608
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