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Cinobufacini Injection Inhibits the Proliferation of Triple-Negative Breast Cancer Through the Pin1–TAZ Signaling Pathway

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer (BC), which is characterized by the total absence of human epidermal growth factor receptor 2 (HER2), progesterone receptor (PR), and estrogen receptor (ER) expression. Cinobufacini injection (CI) is the aqueous extract f...

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Autores principales: Kong, Lu, Liu, Xu, Yu, Bing, Yuan, Ye, Zhao, Qianru, Chen, Yuru, Qu, Bin, Du, Xue, Tian, Xiaoxuan, Shao, Rui, Wang, Yu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9016199/
https://www.ncbi.nlm.nih.gov/pubmed/35450041
http://dx.doi.org/10.3389/fphar.2022.797873
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author Kong, Lu
Liu, Xu
Yu, Bing
Yuan, Ye
Zhao, Qianru
Chen, Yuru
Qu, Bin
Du, Xue
Tian, Xiaoxuan
Shao, Rui
Wang, Yu
author_facet Kong, Lu
Liu, Xu
Yu, Bing
Yuan, Ye
Zhao, Qianru
Chen, Yuru
Qu, Bin
Du, Xue
Tian, Xiaoxuan
Shao, Rui
Wang, Yu
author_sort Kong, Lu
collection PubMed
description Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer (BC), which is characterized by the total absence of human epidermal growth factor receptor 2 (HER2), progesterone receptor (PR), and estrogen receptor (ER) expression. Cinobufacini injection (CI) is the aqueous extract from the dry skin of Bufo gargarizans, which is broadly used for the treatment of malignant tumors. However, the potential mechanism of CI against TNBC has not been fully revealed. In this study, we found that CI inhibited the proliferation of MDA-MB-231 and 4T1 cells in a time- and dose-dependent manner. RNA-seq data showed that downregulated and upregulated genes were mainly enriched in biological processes related to tumor cell proliferation, including cell cycle arrest and regulation of apoptosis signaling pathways. Indeed, after CI treatment, the protein level of CDK1 and Bcl-2/Bax decreased, indicating that CI induced the cell cycle of MDA-MB-231 arrest in the G2/M phase and increased the rate of apoptosis. Meanwhile, CI significantly inhibited the growth of tumor in vivo, and RNA-seq data showed that the TAZ signaling pathway played a vital role after CI treatment. Both immunohistochemistry and Western blot analysis confirmed the downregulation of Pin1 and TAZ, caused by CI treatment. Furthermore, the bioinformatics analysis indicated that Pin1 and TAZ were indeed elevated in TNBC patients, with poor staging, classification, and patient survival rate. In conclusion, CI effectively inhibited the proliferation of TNBC in vitro and in vivo and induced their apoptosis and cycle arrest through the Pin1–TAZ pathway.
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spelling pubmed-90161992022-04-20 Cinobufacini Injection Inhibits the Proliferation of Triple-Negative Breast Cancer Through the Pin1–TAZ Signaling Pathway Kong, Lu Liu, Xu Yu, Bing Yuan, Ye Zhao, Qianru Chen, Yuru Qu, Bin Du, Xue Tian, Xiaoxuan Shao, Rui Wang, Yu Front Pharmacol Pharmacology Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer (BC), which is characterized by the total absence of human epidermal growth factor receptor 2 (HER2), progesterone receptor (PR), and estrogen receptor (ER) expression. Cinobufacini injection (CI) is the aqueous extract from the dry skin of Bufo gargarizans, which is broadly used for the treatment of malignant tumors. However, the potential mechanism of CI against TNBC has not been fully revealed. In this study, we found that CI inhibited the proliferation of MDA-MB-231 and 4T1 cells in a time- and dose-dependent manner. RNA-seq data showed that downregulated and upregulated genes were mainly enriched in biological processes related to tumor cell proliferation, including cell cycle arrest and regulation of apoptosis signaling pathways. Indeed, after CI treatment, the protein level of CDK1 and Bcl-2/Bax decreased, indicating that CI induced the cell cycle of MDA-MB-231 arrest in the G2/M phase and increased the rate of apoptosis. Meanwhile, CI significantly inhibited the growth of tumor in vivo, and RNA-seq data showed that the TAZ signaling pathway played a vital role after CI treatment. Both immunohistochemistry and Western blot analysis confirmed the downregulation of Pin1 and TAZ, caused by CI treatment. Furthermore, the bioinformatics analysis indicated that Pin1 and TAZ were indeed elevated in TNBC patients, with poor staging, classification, and patient survival rate. In conclusion, CI effectively inhibited the proliferation of TNBC in vitro and in vivo and induced their apoptosis and cycle arrest through the Pin1–TAZ pathway. Frontiers Media S.A. 2022-04-05 /pmc/articles/PMC9016199/ /pubmed/35450041 http://dx.doi.org/10.3389/fphar.2022.797873 Text en Copyright © 2022 Kong, Liu, Yu, Yuan, Zhao, Chen, Qu, Du, Tian, Shao and Wang. 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 Pharmacology
Kong, Lu
Liu, Xu
Yu, Bing
Yuan, Ye
Zhao, Qianru
Chen, Yuru
Qu, Bin
Du, Xue
Tian, Xiaoxuan
Shao, Rui
Wang, Yu
Cinobufacini Injection Inhibits the Proliferation of Triple-Negative Breast Cancer Through the Pin1–TAZ Signaling Pathway
title Cinobufacini Injection Inhibits the Proliferation of Triple-Negative Breast Cancer Through the Pin1–TAZ Signaling Pathway
title_full Cinobufacini Injection Inhibits the Proliferation of Triple-Negative Breast Cancer Through the Pin1–TAZ Signaling Pathway
title_fullStr Cinobufacini Injection Inhibits the Proliferation of Triple-Negative Breast Cancer Through the Pin1–TAZ Signaling Pathway
title_full_unstemmed Cinobufacini Injection Inhibits the Proliferation of Triple-Negative Breast Cancer Through the Pin1–TAZ Signaling Pathway
title_short Cinobufacini Injection Inhibits the Proliferation of Triple-Negative Breast Cancer Through the Pin1–TAZ Signaling Pathway
title_sort cinobufacini injection inhibits the proliferation of triple-negative breast cancer through the pin1–taz signaling pathway
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9016199/
https://www.ncbi.nlm.nih.gov/pubmed/35450041
http://dx.doi.org/10.3389/fphar.2022.797873
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