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Inhibition of Rac1 reverses enzalutamide resistance in castration-resistant prostate cancer
Enzalutamide, an androgen receptor inhibitor, has been clinically approved for the treatment of metastatic castration-resistant prostate cancer (CRPC) in the United States. However, patients only benefit from enzalutamide for a short period of time as resistance may develop. Therefore, it is vital t...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
D.A. Spandidos
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7400968/ https://www.ncbi.nlm.nih.gov/pubmed/32782617 http://dx.doi.org/10.3892/ol.2020.11823 |
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author | Chen, Xiaoliang Yin, Lili Qiao, Gan Li, Yanhua Li, Baoyuan Bai, Yunfeng Feng, Feng |
author_facet | Chen, Xiaoliang Yin, Lili Qiao, Gan Li, Yanhua Li, Baoyuan Bai, Yunfeng Feng, Feng |
author_sort | Chen, Xiaoliang |
collection | PubMed |
description | Enzalutamide, an androgen receptor inhibitor, has been clinically approved for the treatment of metastatic castration-resistant prostate cancer (CRPC) in the United States. However, patients only benefit from enzalutamide for a short period of time as resistance may develop. Therefore, it is vital to develop a novel strategy to overcome enzalutamide resistance. Ras-related C3 botulinum toxin substrate 1 (Rac1), which is commonly upregulated in human cancer types, has been recognized as a key molecular component in tumorigenesis, invasion and metastasis. However, the role of Rac1 in enzalutamide-resistance in prostate cancer (PCa) remains unknown. In the present study, Rac1 was demonstrated to be upregulated in enzalutamide-resistant PCa cells, and Rac1 knockdown inhibited enzalutamide-resistant cell proliferation and colony formation. Western blotting results indicated that enzalutamide treatment downregulated the expression levels of JNK and activated transcription factor 2, as well as enhanced the Bax/Bcl-2 ratio and induced cleavage of poly-ADP ribose polymerase. Moreover, knockdown of Rac1 in MR49F cells significantly inhibited cell migration and invasion via the downregulation of Snail and the upregulation of E-cadherin. The results of a nude mouse xenograft tumor model using 22RV1 cells demonstrated that enzalutamide inhibited tumor growth after Rac1 knockdown dramatically, compared to vehicle and single treatment groups. Therefore, the present study provided novel evidence that Rac1 may serve a crucial role in enzalutamide resistance, and that targeting Rac1 may be a potential approach for the treatment of CRPC. |
format | Online Article Text |
id | pubmed-7400968 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | D.A. Spandidos |
record_format | MEDLINE/PubMed |
spelling | pubmed-74009682020-08-10 Inhibition of Rac1 reverses enzalutamide resistance in castration-resistant prostate cancer Chen, Xiaoliang Yin, Lili Qiao, Gan Li, Yanhua Li, Baoyuan Bai, Yunfeng Feng, Feng Oncol Lett Articles Enzalutamide, an androgen receptor inhibitor, has been clinically approved for the treatment of metastatic castration-resistant prostate cancer (CRPC) in the United States. However, patients only benefit from enzalutamide for a short period of time as resistance may develop. Therefore, it is vital to develop a novel strategy to overcome enzalutamide resistance. Ras-related C3 botulinum toxin substrate 1 (Rac1), which is commonly upregulated in human cancer types, has been recognized as a key molecular component in tumorigenesis, invasion and metastasis. However, the role of Rac1 in enzalutamide-resistance in prostate cancer (PCa) remains unknown. In the present study, Rac1 was demonstrated to be upregulated in enzalutamide-resistant PCa cells, and Rac1 knockdown inhibited enzalutamide-resistant cell proliferation and colony formation. Western blotting results indicated that enzalutamide treatment downregulated the expression levels of JNK and activated transcription factor 2, as well as enhanced the Bax/Bcl-2 ratio and induced cleavage of poly-ADP ribose polymerase. Moreover, knockdown of Rac1 in MR49F cells significantly inhibited cell migration and invasion via the downregulation of Snail and the upregulation of E-cadherin. The results of a nude mouse xenograft tumor model using 22RV1 cells demonstrated that enzalutamide inhibited tumor growth after Rac1 knockdown dramatically, compared to vehicle and single treatment groups. Therefore, the present study provided novel evidence that Rac1 may serve a crucial role in enzalutamide resistance, and that targeting Rac1 may be a potential approach for the treatment of CRPC. D.A. Spandidos 2020-09 2020-07-08 /pmc/articles/PMC7400968/ /pubmed/32782617 http://dx.doi.org/10.3892/ol.2020.11823 Text en Copyright: © Chen et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. |
spellingShingle | Articles Chen, Xiaoliang Yin, Lili Qiao, Gan Li, Yanhua Li, Baoyuan Bai, Yunfeng Feng, Feng Inhibition of Rac1 reverses enzalutamide resistance in castration-resistant prostate cancer |
title | Inhibition of Rac1 reverses enzalutamide resistance in castration-resistant prostate cancer |
title_full | Inhibition of Rac1 reverses enzalutamide resistance in castration-resistant prostate cancer |
title_fullStr | Inhibition of Rac1 reverses enzalutamide resistance in castration-resistant prostate cancer |
title_full_unstemmed | Inhibition of Rac1 reverses enzalutamide resistance in castration-resistant prostate cancer |
title_short | Inhibition of Rac1 reverses enzalutamide resistance in castration-resistant prostate cancer |
title_sort | inhibition of rac1 reverses enzalutamide resistance in castration-resistant prostate cancer |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7400968/ https://www.ncbi.nlm.nih.gov/pubmed/32782617 http://dx.doi.org/10.3892/ol.2020.11823 |
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