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Overcoming chemoresistance in prostate cancer with Chinese medicine Tripterygium wilfordii via multiple mechanisms
A leading cause of cancer chemotherapy failure is chemoresistance, which often involves multiple mechanisms. Chinese medicines (CM) usually contain multiple components which could potentially target many mechanisms simultaneously and may offer an advantage over single compounds that target one mecha...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5308648/ https://www.ncbi.nlm.nih.gov/pubmed/27487134 http://dx.doi.org/10.18632/oncotarget.10868 |
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author | Wang, Zhijun Ravula, Ranadheer Shi, Leming Song, Yunjie Yeung, Steven Liu, Mandy Lau, Bernard Hao, Jijun Wang, Jeffrey Lam, Christopher Wai Kei Chow, Moses Sing Sum Huang, Ying |
author_facet | Wang, Zhijun Ravula, Ranadheer Shi, Leming Song, Yunjie Yeung, Steven Liu, Mandy Lau, Bernard Hao, Jijun Wang, Jeffrey Lam, Christopher Wai Kei Chow, Moses Sing Sum Huang, Ying |
author_sort | Wang, Zhijun |
collection | PubMed |
description | A leading cause of cancer chemotherapy failure is chemoresistance, which often involves multiple mechanisms. Chinese medicines (CM) usually contain multiple components which could potentially target many mechanisms simultaneously and may offer an advantage over single compounds that target one mechanism at a time. The purpose of this study was to investigate the chemosensitizing effect (CE) of a specific CM, Tripterygium wilfordii (TW), on prostate cancer cells resistant to docetaxel (Dtx) and identify the potential mechanisms. The CE of TW (in combination with Dtx) was evaluated in two Dtx resistant prostate cancer cell lines (PC3-TxR and DU145-TxR) and the efficacy of the combination for resistant PC3-TxR tumor was investigated using a xenograft mouse model. For mechanistic study, the inhibitory effect of TW on P-glycoprotein activity was assessed. In addition, novel gene targets of TW were identified using DNA microarray and quantitative PCR. Results showed that TW induced a CE of 8 and >38 folds in PC3-TxR and DU145-TxR cells, respectively with Dtx IC(50) reversed back to that of the sensitive parent cells. An optimum dose of TW+Dtx significantly retarded tumor growth in mice compared to TW or Dtx alone. TW inhibited P-glycoprotein activity and induced a significant gene expression changes in genes related to angiogenesis, cell cycle regulation and differentiation. Our in vitro and in vivo studies demonstrate that TW in combination with Dtx was able to overcome the chemoresistance and suppress resistant prostate tumor growth via multi-mechanisms. |
format | Online Article Text |
id | pubmed-5308648 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-53086482017-03-09 Overcoming chemoresistance in prostate cancer with Chinese medicine Tripterygium wilfordii via multiple mechanisms Wang, Zhijun Ravula, Ranadheer Shi, Leming Song, Yunjie Yeung, Steven Liu, Mandy Lau, Bernard Hao, Jijun Wang, Jeffrey Lam, Christopher Wai Kei Chow, Moses Sing Sum Huang, Ying Oncotarget Research Paper A leading cause of cancer chemotherapy failure is chemoresistance, which often involves multiple mechanisms. Chinese medicines (CM) usually contain multiple components which could potentially target many mechanisms simultaneously and may offer an advantage over single compounds that target one mechanism at a time. The purpose of this study was to investigate the chemosensitizing effect (CE) of a specific CM, Tripterygium wilfordii (TW), on prostate cancer cells resistant to docetaxel (Dtx) and identify the potential mechanisms. The CE of TW (in combination with Dtx) was evaluated in two Dtx resistant prostate cancer cell lines (PC3-TxR and DU145-TxR) and the efficacy of the combination for resistant PC3-TxR tumor was investigated using a xenograft mouse model. For mechanistic study, the inhibitory effect of TW on P-glycoprotein activity was assessed. In addition, novel gene targets of TW were identified using DNA microarray and quantitative PCR. Results showed that TW induced a CE of 8 and >38 folds in PC3-TxR and DU145-TxR cells, respectively with Dtx IC(50) reversed back to that of the sensitive parent cells. An optimum dose of TW+Dtx significantly retarded tumor growth in mice compared to TW or Dtx alone. TW inhibited P-glycoprotein activity and induced a significant gene expression changes in genes related to angiogenesis, cell cycle regulation and differentiation. Our in vitro and in vivo studies demonstrate that TW in combination with Dtx was able to overcome the chemoresistance and suppress resistant prostate tumor growth via multi-mechanisms. Impact Journals LLC 2016-07-28 /pmc/articles/PMC5308648/ /pubmed/27487134 http://dx.doi.org/10.18632/oncotarget.10868 Text en Copyright: © 2016 Wang et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Wang, Zhijun Ravula, Ranadheer Shi, Leming Song, Yunjie Yeung, Steven Liu, Mandy Lau, Bernard Hao, Jijun Wang, Jeffrey Lam, Christopher Wai Kei Chow, Moses Sing Sum Huang, Ying Overcoming chemoresistance in prostate cancer with Chinese medicine Tripterygium wilfordii via multiple mechanisms |
title | Overcoming chemoresistance in prostate cancer with Chinese medicine Tripterygium wilfordii via multiple mechanisms |
title_full | Overcoming chemoresistance in prostate cancer with Chinese medicine Tripterygium wilfordii via multiple mechanisms |
title_fullStr | Overcoming chemoresistance in prostate cancer with Chinese medicine Tripterygium wilfordii via multiple mechanisms |
title_full_unstemmed | Overcoming chemoresistance in prostate cancer with Chinese medicine Tripterygium wilfordii via multiple mechanisms |
title_short | Overcoming chemoresistance in prostate cancer with Chinese medicine Tripterygium wilfordii via multiple mechanisms |
title_sort | overcoming chemoresistance in prostate cancer with chinese medicine tripterygium wilfordii via multiple mechanisms |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5308648/ https://www.ncbi.nlm.nih.gov/pubmed/27487134 http://dx.doi.org/10.18632/oncotarget.10868 |
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