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The Chemopreventive Role of β-Elemene in Cholangiocarcinoma by Restoring PCDH9 Expression

BACKGROUND: β-Elemene, an effective anticancer component isolated from the Chinese herbal medicine Rhizoma Zedoariae, has been proved to have therapeutic potential against multiple cancers by extensive clinical trials and experimental research. However, its preventive role in cholangiocarcinoma (CCA...

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Autores principales: Wu, Qing, Shi, Xintong, Pan, Yating, Liao, Xinyi, Xu, Jiahua, Gu, Xiaoqiang, Yu, Wenlong, Chen, Ying, Yu, Guanzhen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9314746/
https://www.ncbi.nlm.nih.gov/pubmed/35903688
http://dx.doi.org/10.3389/fonc.2022.874457
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author Wu, Qing
Shi, Xintong
Pan, Yating
Liao, Xinyi
Xu, Jiahua
Gu, Xiaoqiang
Yu, Wenlong
Chen, Ying
Yu, Guanzhen
author_facet Wu, Qing
Shi, Xintong
Pan, Yating
Liao, Xinyi
Xu, Jiahua
Gu, Xiaoqiang
Yu, Wenlong
Chen, Ying
Yu, Guanzhen
author_sort Wu, Qing
collection PubMed
description BACKGROUND: β-Elemene, an effective anticancer component isolated from the Chinese herbal medicine Rhizoma Zedoariae, has been proved to have therapeutic potential against multiple cancers by extensive clinical trials and experimental research. However, its preventive role in cholangiocarcinoma (CCA) and the mechanisms of action of β-elemene on CCA need to be further investigated. METHODS: A thioacetamide (TAA)-induced pre-CCA animal model was well-established, and a low dosage of β-elemene was intragastrically (i.g.) administered for 6 months. Livers were harvested and examined histologically by a deep-learning convolutional neural network (CNN). cDNA array was used to analyze the genetic changes of CCA cells following β-elemene treatment. Immunohistochemical methods were applied to detect β-elemene-targeted protein PCDH9 in CCA specimens, and its predictive role was analyzed. β-Elemene treatment at the cellular or animal level was performed to test the effect of this traditional Chinese medicine on CCA cells. RESULTS: In the rat model of pre-CCA, the ratio of cholangiolar proliferation lesions was 0.98% ± 0.72% in the control group, significantly higher than that of the β-elemene (0. 47% ± 0.30%) groups (p = 0.0471). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that the top 10 pathways affected by β-elemene treatment were associated with energy metabolism, and one was associated with the cell cycle. β-Elemene inactivated a number of oncogenes and restored the expression of multiple tumor suppressors. PCDH9 is a target of β-elemene and displays an important role in predicting tumor recurrence in CCA patients. CONCLUSIONS: These findings proved that long-term use of β-elemene has the potential to interrupt the progression of CCA and improve the life quality of rats. Moreover, β-elemene exerted its anticancer potential partially by restoring the expression of PCDH9.
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spelling pubmed-93147462022-07-27 The Chemopreventive Role of β-Elemene in Cholangiocarcinoma by Restoring PCDH9 Expression Wu, Qing Shi, Xintong Pan, Yating Liao, Xinyi Xu, Jiahua Gu, Xiaoqiang Yu, Wenlong Chen, Ying Yu, Guanzhen Front Oncol Oncology BACKGROUND: β-Elemene, an effective anticancer component isolated from the Chinese herbal medicine Rhizoma Zedoariae, has been proved to have therapeutic potential against multiple cancers by extensive clinical trials and experimental research. However, its preventive role in cholangiocarcinoma (CCA) and the mechanisms of action of β-elemene on CCA need to be further investigated. METHODS: A thioacetamide (TAA)-induced pre-CCA animal model was well-established, and a low dosage of β-elemene was intragastrically (i.g.) administered for 6 months. Livers were harvested and examined histologically by a deep-learning convolutional neural network (CNN). cDNA array was used to analyze the genetic changes of CCA cells following β-elemene treatment. Immunohistochemical methods were applied to detect β-elemene-targeted protein PCDH9 in CCA specimens, and its predictive role was analyzed. β-Elemene treatment at the cellular or animal level was performed to test the effect of this traditional Chinese medicine on CCA cells. RESULTS: In the rat model of pre-CCA, the ratio of cholangiolar proliferation lesions was 0.98% ± 0.72% in the control group, significantly higher than that of the β-elemene (0. 47% ± 0.30%) groups (p = 0.0471). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that the top 10 pathways affected by β-elemene treatment were associated with energy metabolism, and one was associated with the cell cycle. β-Elemene inactivated a number of oncogenes and restored the expression of multiple tumor suppressors. PCDH9 is a target of β-elemene and displays an important role in predicting tumor recurrence in CCA patients. CONCLUSIONS: These findings proved that long-term use of β-elemene has the potential to interrupt the progression of CCA and improve the life quality of rats. Moreover, β-elemene exerted its anticancer potential partially by restoring the expression of PCDH9. Frontiers Media S.A. 2022-07-12 /pmc/articles/PMC9314746/ /pubmed/35903688 http://dx.doi.org/10.3389/fonc.2022.874457 Text en Copyright © 2022 Wu, Shi, Pan, Liao, Xu, Gu, Yu, Chen and Yu https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Wu, Qing
Shi, Xintong
Pan, Yating
Liao, Xinyi
Xu, Jiahua
Gu, Xiaoqiang
Yu, Wenlong
Chen, Ying
Yu, Guanzhen
The Chemopreventive Role of β-Elemene in Cholangiocarcinoma by Restoring PCDH9 Expression
title The Chemopreventive Role of β-Elemene in Cholangiocarcinoma by Restoring PCDH9 Expression
title_full The Chemopreventive Role of β-Elemene in Cholangiocarcinoma by Restoring PCDH9 Expression
title_fullStr The Chemopreventive Role of β-Elemene in Cholangiocarcinoma by Restoring PCDH9 Expression
title_full_unstemmed The Chemopreventive Role of β-Elemene in Cholangiocarcinoma by Restoring PCDH9 Expression
title_short The Chemopreventive Role of β-Elemene in Cholangiocarcinoma by Restoring PCDH9 Expression
title_sort chemopreventive role of β-elemene in cholangiocarcinoma by restoring pcdh9 expression
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9314746/
https://www.ncbi.nlm.nih.gov/pubmed/35903688
http://dx.doi.org/10.3389/fonc.2022.874457
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