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Treatment with docetaxel in combination with Aneustat leads to potent inhibition of metastasis in a patient-derived xenograft model of advanced prostate cancer

BACKGROUND: Docetaxel used for first-line treatment of advanced prostate cancer (PCa) is only marginally effective. We previously showed, using the LTL-313H subrenal capsule patient-derived metastatic PCa xenograft model, that docetaxel combined with Aneustat (OMN54), a multivalent plant-derived the...

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Autores principales: Qu, Sifeng, Ci, Xinpei, Xue, Hui, Dong, Xin, Hao, Jun, Lin, Dong, Clermont, Pier-Luc, Wu, Rebecca, Collins, Colin C, Gout, Peter W, Wang, Yuzhuo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5877435/
https://www.ncbi.nlm.nih.gov/pubmed/29381682
http://dx.doi.org/10.1038/bjc.2017.474
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author Qu, Sifeng
Ci, Xinpei
Xue, Hui
Dong, Xin
Hao, Jun
Lin, Dong
Clermont, Pier-Luc
Wu, Rebecca
Collins, Colin C
Gout, Peter W
Wang, Yuzhuo
author_facet Qu, Sifeng
Ci, Xinpei
Xue, Hui
Dong, Xin
Hao, Jun
Lin, Dong
Clermont, Pier-Luc
Wu, Rebecca
Collins, Colin C
Gout, Peter W
Wang, Yuzhuo
author_sort Qu, Sifeng
collection PubMed
description BACKGROUND: Docetaxel used for first-line treatment of advanced prostate cancer (PCa) is only marginally effective. We previously showed, using the LTL-313H subrenal capsule patient-derived metastatic PCa xenograft model, that docetaxel combined with Aneustat (OMN54), a multivalent plant-derived therapeutic, led to marked synergistic tumour growth inhibition. Here, we investigated the effect of docetaxel+Aneustat on metastasis. METHODS: C4-2 cells were incubated with docetaxel, Aneustat and docetaxel+Aneustat to assess effects on cell migration. The LTL-313H model, similarly treated, was analysed for effects on lung micro-metastasis and kidney invasion. The LTL-313H gene expression profile was compared with profiles of PCa patients (obtained from Oncomine) and subjected to IPA to determine involvement of cancer driver genes. RESULTS: Docetaxel+Aneustat markedly inhibited C4-2 cell migration and LTL-313H lung micro-metastasis/kidney invasion. Oncomine analysis indicated that treatment with docetaxel+Aneustat was associated with improved patient outcome. The drug combination markedly downregulated expression of cancer driver genes such as FOXM1 (and FOXM1-target genes). FOXM1 overexpression reduced the anti-metastatic activity of docetaxel+Aneustat. CONCLUSIONS: Docetaxel+Aneustat can inhibit PCa tissue invasion and metastasis. This activity appears to be based on reduced expression of cancer driver genes such as FOXM1. Use of docetaxel+Aneustat may provide a new, more effective regimen for therapy of metastatic PCa.
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spelling pubmed-58774352018-04-04 Treatment with docetaxel in combination with Aneustat leads to potent inhibition of metastasis in a patient-derived xenograft model of advanced prostate cancer Qu, Sifeng Ci, Xinpei Xue, Hui Dong, Xin Hao, Jun Lin, Dong Clermont, Pier-Luc Wu, Rebecca Collins, Colin C Gout, Peter W Wang, Yuzhuo Br J Cancer Translational Therapeutics BACKGROUND: Docetaxel used for first-line treatment of advanced prostate cancer (PCa) is only marginally effective. We previously showed, using the LTL-313H subrenal capsule patient-derived metastatic PCa xenograft model, that docetaxel combined with Aneustat (OMN54), a multivalent plant-derived therapeutic, led to marked synergistic tumour growth inhibition. Here, we investigated the effect of docetaxel+Aneustat on metastasis. METHODS: C4-2 cells were incubated with docetaxel, Aneustat and docetaxel+Aneustat to assess effects on cell migration. The LTL-313H model, similarly treated, was analysed for effects on lung micro-metastasis and kidney invasion. The LTL-313H gene expression profile was compared with profiles of PCa patients (obtained from Oncomine) and subjected to IPA to determine involvement of cancer driver genes. RESULTS: Docetaxel+Aneustat markedly inhibited C4-2 cell migration and LTL-313H lung micro-metastasis/kidney invasion. Oncomine analysis indicated that treatment with docetaxel+Aneustat was associated with improved patient outcome. The drug combination markedly downregulated expression of cancer driver genes such as FOXM1 (and FOXM1-target genes). FOXM1 overexpression reduced the anti-metastatic activity of docetaxel+Aneustat. CONCLUSIONS: Docetaxel+Aneustat can inhibit PCa tissue invasion and metastasis. This activity appears to be based on reduced expression of cancer driver genes such as FOXM1. Use of docetaxel+Aneustat may provide a new, more effective regimen for therapy of metastatic PCa. Nature Publishing Group 2018-03-20 2018-01-30 /pmc/articles/PMC5877435/ /pubmed/29381682 http://dx.doi.org/10.1038/bjc.2017.474 Text en Copyright © 2018 The Author(s) http://creativecommons.org/licenses/by-nc-sa/4.0/ This work is licensed under the Creative Commons Attribution-Non-Commercial-Share Alike 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/4.0/
spellingShingle Translational Therapeutics
Qu, Sifeng
Ci, Xinpei
Xue, Hui
Dong, Xin
Hao, Jun
Lin, Dong
Clermont, Pier-Luc
Wu, Rebecca
Collins, Colin C
Gout, Peter W
Wang, Yuzhuo
Treatment with docetaxel in combination with Aneustat leads to potent inhibition of metastasis in a patient-derived xenograft model of advanced prostate cancer
title Treatment with docetaxel in combination with Aneustat leads to potent inhibition of metastasis in a patient-derived xenograft model of advanced prostate cancer
title_full Treatment with docetaxel in combination with Aneustat leads to potent inhibition of metastasis in a patient-derived xenograft model of advanced prostate cancer
title_fullStr Treatment with docetaxel in combination with Aneustat leads to potent inhibition of metastasis in a patient-derived xenograft model of advanced prostate cancer
title_full_unstemmed Treatment with docetaxel in combination with Aneustat leads to potent inhibition of metastasis in a patient-derived xenograft model of advanced prostate cancer
title_short Treatment with docetaxel in combination with Aneustat leads to potent inhibition of metastasis in a patient-derived xenograft model of advanced prostate cancer
title_sort treatment with docetaxel in combination with aneustat leads to potent inhibition of metastasis in a patient-derived xenograft model of advanced prostate cancer
topic Translational Therapeutics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5877435/
https://www.ncbi.nlm.nih.gov/pubmed/29381682
http://dx.doi.org/10.1038/bjc.2017.474
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