Cargando…

Atractylenolide-I Sensitizes Triple-Negative Breast Cancer Cells to Paclitaxel by Blocking CTGF Expression and Fibroblast Activation

This investigation was conducted to elucidate whether atractylenolide-I (ATL-1), which is the main component of Atractylodes macrocephala Koidz, can sensitize triple-negative breast cancer (TNBC) cells to paclitaxel and investigate the possible mechanism involved. We discovered that ATL-1 could inhi...

Descripción completa

Detalles Bibliográficos
Autores principales: Wang, Meng, Li, Xue-Zhen, Zhang, Ming-Xing, Ye, Qian-Yu, Chen, Ying-Xia, Chang, Xu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8526898/
https://www.ncbi.nlm.nih.gov/pubmed/34692516
http://dx.doi.org/10.3389/fonc.2021.738534
_version_ 1784585962229071872
author Wang, Meng
Li, Xue-Zhen
Zhang, Ming-Xing
Ye, Qian-Yu
Chen, Ying-Xia
Chang, Xu
author_facet Wang, Meng
Li, Xue-Zhen
Zhang, Ming-Xing
Ye, Qian-Yu
Chen, Ying-Xia
Chang, Xu
author_sort Wang, Meng
collection PubMed
description This investigation was conducted to elucidate whether atractylenolide-I (ATL-1), which is the main component of Atractylodes macrocephala Koidz, can sensitize triple-negative breast cancer (TNBC) cells to paclitaxel and investigate the possible mechanism involved. We discovered that ATL-1 could inhibit tumor cell migration and increase the sensitivity of tumor cells to paclitaxel. ATL-1 downregulated the expression and secretion of CTGF in TNBC cells. Apart from inhibiting TNBC cell migration via CTGF, ATL-1 downregulated the expression of CTGF in fibroblasts and decreased the ability of breast cancer cells to transform fibroblasts into cancer-associated fibroblasts (CAFs), which in turn increased the sensitivity of TNBC cells to paclitaxel. In a mouse model, we found that ATL-1 treatments could enhance the chemotherapeutic effect of paclitaxel on tumors and reduce tumor metastasis to the lungs and liver. Primary cultured fibroblasts derived from inoculated tumors in mice treated with ATL-1 combined with paclitaxel expressed relatively low levels of CAF markers. Collectively, our data indicate that ATL-1 can sensitize TNBC cells to paclitaxel by blocking CTGF expression and fibroblast activation and could be helpful in future research to determine the value of ATL-1 in the clinical setting.
format Online
Article
Text
id pubmed-8526898
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-85268982021-10-21 Atractylenolide-I Sensitizes Triple-Negative Breast Cancer Cells to Paclitaxel by Blocking CTGF Expression and Fibroblast Activation Wang, Meng Li, Xue-Zhen Zhang, Ming-Xing Ye, Qian-Yu Chen, Ying-Xia Chang, Xu Front Oncol Oncology This investigation was conducted to elucidate whether atractylenolide-I (ATL-1), which is the main component of Atractylodes macrocephala Koidz, can sensitize triple-negative breast cancer (TNBC) cells to paclitaxel and investigate the possible mechanism involved. We discovered that ATL-1 could inhibit tumor cell migration and increase the sensitivity of tumor cells to paclitaxel. ATL-1 downregulated the expression and secretion of CTGF in TNBC cells. Apart from inhibiting TNBC cell migration via CTGF, ATL-1 downregulated the expression of CTGF in fibroblasts and decreased the ability of breast cancer cells to transform fibroblasts into cancer-associated fibroblasts (CAFs), which in turn increased the sensitivity of TNBC cells to paclitaxel. In a mouse model, we found that ATL-1 treatments could enhance the chemotherapeutic effect of paclitaxel on tumors and reduce tumor metastasis to the lungs and liver. Primary cultured fibroblasts derived from inoculated tumors in mice treated with ATL-1 combined with paclitaxel expressed relatively low levels of CAF markers. Collectively, our data indicate that ATL-1 can sensitize TNBC cells to paclitaxel by blocking CTGF expression and fibroblast activation and could be helpful in future research to determine the value of ATL-1 in the clinical setting. Frontiers Media S.A. 2021-10-06 /pmc/articles/PMC8526898/ /pubmed/34692516 http://dx.doi.org/10.3389/fonc.2021.738534 Text en Copyright © 2021 Wang, Li, Zhang, Ye, Chen and Chang 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
Wang, Meng
Li, Xue-Zhen
Zhang, Ming-Xing
Ye, Qian-Yu
Chen, Ying-Xia
Chang, Xu
Atractylenolide-I Sensitizes Triple-Negative Breast Cancer Cells to Paclitaxel by Blocking CTGF Expression and Fibroblast Activation
title Atractylenolide-I Sensitizes Triple-Negative Breast Cancer Cells to Paclitaxel by Blocking CTGF Expression and Fibroblast Activation
title_full Atractylenolide-I Sensitizes Triple-Negative Breast Cancer Cells to Paclitaxel by Blocking CTGF Expression and Fibroblast Activation
title_fullStr Atractylenolide-I Sensitizes Triple-Negative Breast Cancer Cells to Paclitaxel by Blocking CTGF Expression and Fibroblast Activation
title_full_unstemmed Atractylenolide-I Sensitizes Triple-Negative Breast Cancer Cells to Paclitaxel by Blocking CTGF Expression and Fibroblast Activation
title_short Atractylenolide-I Sensitizes Triple-Negative Breast Cancer Cells to Paclitaxel by Blocking CTGF Expression and Fibroblast Activation
title_sort atractylenolide-i sensitizes triple-negative breast cancer cells to paclitaxel by blocking ctgf expression and fibroblast activation
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8526898/
https://www.ncbi.nlm.nih.gov/pubmed/34692516
http://dx.doi.org/10.3389/fonc.2021.738534
work_keys_str_mv AT wangmeng atractylenolideisensitizestriplenegativebreastcancercellstopaclitaxelbyblockingctgfexpressionandfibroblastactivation
AT lixuezhen atractylenolideisensitizestriplenegativebreastcancercellstopaclitaxelbyblockingctgfexpressionandfibroblastactivation
AT zhangmingxing atractylenolideisensitizestriplenegativebreastcancercellstopaclitaxelbyblockingctgfexpressionandfibroblastactivation
AT yeqianyu atractylenolideisensitizestriplenegativebreastcancercellstopaclitaxelbyblockingctgfexpressionandfibroblastactivation
AT chenyingxia atractylenolideisensitizestriplenegativebreastcancercellstopaclitaxelbyblockingctgfexpressionandfibroblastactivation
AT changxu atractylenolideisensitizestriplenegativebreastcancercellstopaclitaxelbyblockingctgfexpressionandfibroblastactivation