Cargando…

SOX8 Knockdown Overcomes Enzalutamide Resistance in Castration-Resistant Prostate Cancer by Inhibiting the Notch Signaling Pathway

Castration-resistant prostate cancer (CRPC) is still challenging to treat. Dissatisfaction with androgen signal-targeted therapy forces people to look for other treatment strategies. Therefore, this study is aimed at exploring the role of SOX8/Notch signaling in CRPC. The upregulation of SOX8, Notch...

Descripción completa

Detalles Bibliográficos
Autores principales: Du, Zhongbo, Chen, Xiaobin, Zhu, Pingyu, Sun, Wei, Lv, Qi, Cheng, Shulin, Yang, Xuesong, Yu, Xiaodong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9560839/
https://www.ncbi.nlm.nih.gov/pubmed/36246971
http://dx.doi.org/10.1155/2022/9235837
_version_ 1784807841053278208
author Du, Zhongbo
Chen, Xiaobin
Zhu, Pingyu
Sun, Wei
Lv, Qi
Cheng, Shulin
Yang, Xuesong
Yu, Xiaodong
author_facet Du, Zhongbo
Chen, Xiaobin
Zhu, Pingyu
Sun, Wei
Lv, Qi
Cheng, Shulin
Yang, Xuesong
Yu, Xiaodong
author_sort Du, Zhongbo
collection PubMed
description Castration-resistant prostate cancer (CRPC) is still challenging to treat. Dissatisfaction with androgen signal-targeted therapy forces people to look for other treatment strategies. Therefore, this study is aimed at exploring the role of SOX8/Notch signaling in CRPC. The upregulation of SOX8, Notch4, and Hes5 indicated a poor progression-free survival (PFS) in CRPC patients. The expression of these proteins was also upregulated in enzalutamide-resistant LNCaP cells (Enza-R). Moreover, knocking down SOX8 inhibited malignant biological behaviors and decreased the activation of Notch signaling in Enza-R cells. Importantly, knocking down SOX8 obviously reversed the enzalutamide resistance in Enza-R cells, while RO0429097 (a γ secretase inhibitor inactivates Notch signaling) exerted similar effects. At last, we found that both SOX8 knockdown and/or RO0429097 suppressed tumor growth and bone metastasis in vivo. Altogether, our study indicated that the SOX8/Notch signaling is involved in CRPC and that these enzymes are possible targets to develop novel treatment for CRPC.
format Online
Article
Text
id pubmed-9560839
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Hindawi
record_format MEDLINE/PubMed
spelling pubmed-95608392022-10-14 SOX8 Knockdown Overcomes Enzalutamide Resistance in Castration-Resistant Prostate Cancer by Inhibiting the Notch Signaling Pathway Du, Zhongbo Chen, Xiaobin Zhu, Pingyu Sun, Wei Lv, Qi Cheng, Shulin Yang, Xuesong Yu, Xiaodong Biomed Res Int Research Article Castration-resistant prostate cancer (CRPC) is still challenging to treat. Dissatisfaction with androgen signal-targeted therapy forces people to look for other treatment strategies. Therefore, this study is aimed at exploring the role of SOX8/Notch signaling in CRPC. The upregulation of SOX8, Notch4, and Hes5 indicated a poor progression-free survival (PFS) in CRPC patients. The expression of these proteins was also upregulated in enzalutamide-resistant LNCaP cells (Enza-R). Moreover, knocking down SOX8 inhibited malignant biological behaviors and decreased the activation of Notch signaling in Enza-R cells. Importantly, knocking down SOX8 obviously reversed the enzalutamide resistance in Enza-R cells, while RO0429097 (a γ secretase inhibitor inactivates Notch signaling) exerted similar effects. At last, we found that both SOX8 knockdown and/or RO0429097 suppressed tumor growth and bone metastasis in vivo. Altogether, our study indicated that the SOX8/Notch signaling is involved in CRPC and that these enzymes are possible targets to develop novel treatment for CRPC. Hindawi 2022-10-06 /pmc/articles/PMC9560839/ /pubmed/36246971 http://dx.doi.org/10.1155/2022/9235837 Text en Copyright © 2022 Zhongbo Du et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Du, Zhongbo
Chen, Xiaobin
Zhu, Pingyu
Sun, Wei
Lv, Qi
Cheng, Shulin
Yang, Xuesong
Yu, Xiaodong
SOX8 Knockdown Overcomes Enzalutamide Resistance in Castration-Resistant Prostate Cancer by Inhibiting the Notch Signaling Pathway
title SOX8 Knockdown Overcomes Enzalutamide Resistance in Castration-Resistant Prostate Cancer by Inhibiting the Notch Signaling Pathway
title_full SOX8 Knockdown Overcomes Enzalutamide Resistance in Castration-Resistant Prostate Cancer by Inhibiting the Notch Signaling Pathway
title_fullStr SOX8 Knockdown Overcomes Enzalutamide Resistance in Castration-Resistant Prostate Cancer by Inhibiting the Notch Signaling Pathway
title_full_unstemmed SOX8 Knockdown Overcomes Enzalutamide Resistance in Castration-Resistant Prostate Cancer by Inhibiting the Notch Signaling Pathway
title_short SOX8 Knockdown Overcomes Enzalutamide Resistance in Castration-Resistant Prostate Cancer by Inhibiting the Notch Signaling Pathway
title_sort sox8 knockdown overcomes enzalutamide resistance in castration-resistant prostate cancer by inhibiting the notch signaling pathway
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9560839/
https://www.ncbi.nlm.nih.gov/pubmed/36246971
http://dx.doi.org/10.1155/2022/9235837
work_keys_str_mv AT duzhongbo sox8knockdownovercomesenzalutamideresistanceincastrationresistantprostatecancerbyinhibitingthenotchsignalingpathway
AT chenxiaobin sox8knockdownovercomesenzalutamideresistanceincastrationresistantprostatecancerbyinhibitingthenotchsignalingpathway
AT zhupingyu sox8knockdownovercomesenzalutamideresistanceincastrationresistantprostatecancerbyinhibitingthenotchsignalingpathway
AT sunwei sox8knockdownovercomesenzalutamideresistanceincastrationresistantprostatecancerbyinhibitingthenotchsignalingpathway
AT lvqi sox8knockdownovercomesenzalutamideresistanceincastrationresistantprostatecancerbyinhibitingthenotchsignalingpathway
AT chengshulin sox8knockdownovercomesenzalutamideresistanceincastrationresistantprostatecancerbyinhibitingthenotchsignalingpathway
AT yangxuesong sox8knockdownovercomesenzalutamideresistanceincastrationresistantprostatecancerbyinhibitingthenotchsignalingpathway
AT yuxiaodong sox8knockdownovercomesenzalutamideresistanceincastrationresistantprostatecancerbyinhibitingthenotchsignalingpathway