Cargando…
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...
Autores principales: | , , , , , , , , |
---|---|
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 |
_version_ | 1784754391548428288 |
---|---|
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. |
format | Online Article Text |
id | pubmed-9314746 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT wuqing thechemopreventiveroleofbelemeneincholangiocarcinomabyrestoringpcdh9expression AT shixintong thechemopreventiveroleofbelemeneincholangiocarcinomabyrestoringpcdh9expression AT panyating thechemopreventiveroleofbelemeneincholangiocarcinomabyrestoringpcdh9expression AT liaoxinyi thechemopreventiveroleofbelemeneincholangiocarcinomabyrestoringpcdh9expression AT xujiahua thechemopreventiveroleofbelemeneincholangiocarcinomabyrestoringpcdh9expression AT guxiaoqiang thechemopreventiveroleofbelemeneincholangiocarcinomabyrestoringpcdh9expression AT yuwenlong thechemopreventiveroleofbelemeneincholangiocarcinomabyrestoringpcdh9expression AT chenying thechemopreventiveroleofbelemeneincholangiocarcinomabyrestoringpcdh9expression AT yuguanzhen thechemopreventiveroleofbelemeneincholangiocarcinomabyrestoringpcdh9expression AT wuqing chemopreventiveroleofbelemeneincholangiocarcinomabyrestoringpcdh9expression AT shixintong chemopreventiveroleofbelemeneincholangiocarcinomabyrestoringpcdh9expression AT panyating chemopreventiveroleofbelemeneincholangiocarcinomabyrestoringpcdh9expression AT liaoxinyi chemopreventiveroleofbelemeneincholangiocarcinomabyrestoringpcdh9expression AT xujiahua chemopreventiveroleofbelemeneincholangiocarcinomabyrestoringpcdh9expression AT guxiaoqiang chemopreventiveroleofbelemeneincholangiocarcinomabyrestoringpcdh9expression AT yuwenlong chemopreventiveroleofbelemeneincholangiocarcinomabyrestoringpcdh9expression AT chenying chemopreventiveroleofbelemeneincholangiocarcinomabyrestoringpcdh9expression AT yuguanzhen chemopreventiveroleofbelemeneincholangiocarcinomabyrestoringpcdh9expression |