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Cordycepin Inhibits Growth and Metastasis Formation of MDA-MB-231 Xenografts in Nude Mice by Modulating the Hedgehog Pathway

We previously found that cordycepin inhibits the growth and metastasis formation of MDA-MB-231 cells through the Hedgehog pathway but has not validated this in vivo. In this study, we confirmed cordycepin’s anti-triple-negative breast cancer (TNBC) effect in nude mice and documented its mechanism. W...

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Autores principales: Wu, Wenya, Li, Xiaomin, Qi, Meng, Hu, Xin, Cao, Fenghua, Wu, Xiaoping, Fu, Junsheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9499653/
https://www.ncbi.nlm.nih.gov/pubmed/36142286
http://dx.doi.org/10.3390/ijms231810362
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author Wu, Wenya
Li, Xiaomin
Qi, Meng
Hu, Xin
Cao, Fenghua
Wu, Xiaoping
Fu, Junsheng
author_facet Wu, Wenya
Li, Xiaomin
Qi, Meng
Hu, Xin
Cao, Fenghua
Wu, Xiaoping
Fu, Junsheng
author_sort Wu, Wenya
collection PubMed
description We previously found that cordycepin inhibits the growth and metastasis formation of MDA-MB-231 cells through the Hedgehog pathway but has not validated this in vivo. In this study, we confirmed cordycepin’s anti-triple-negative breast cancer (TNBC) effect in nude mice and documented its mechanism. We found that cordycepin reduced the volume and weight of MDA-MB-231 xenografts and affected the expression of proliferation-, apoptosis-, epithelial–mesenchymal transition-, and matrix metalloproteinase-related proteins without side effects. RNA sequencing screening, pathway enrichment, and the protein network interaction analysis revealed enriched pathways and targets mainly concentrated on the Hedgehog pathway and its core components of SHH and GLI2. This indicates that the Hedgehog pathway plays a central role in the cordycepin-mediated regulation of growth and metastasis formation in TNBC. The database analysis of the Hedgehog pathway markers (SHH, PTCH1, SMO, GLI1, and GLI2) revealed that the Hedgehog pathway is activated in breast cancer tissues, and its high expression is not conducive to a patient’s survival. Finally, we verified that cordycepin effectively inhibited the Hedgehog pathway in TNBC through Western blotting and immunohistochemistry. This study found that cordycepin could regulate the growth and metastasis formation of TNBC through the Hedgehog pathway in vivo, which provides new insights for targeting and treating breast cancer.
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spelling pubmed-94996532022-09-23 Cordycepin Inhibits Growth and Metastasis Formation of MDA-MB-231 Xenografts in Nude Mice by Modulating the Hedgehog Pathway Wu, Wenya Li, Xiaomin Qi, Meng Hu, Xin Cao, Fenghua Wu, Xiaoping Fu, Junsheng Int J Mol Sci Article We previously found that cordycepin inhibits the growth and metastasis formation of MDA-MB-231 cells through the Hedgehog pathway but has not validated this in vivo. In this study, we confirmed cordycepin’s anti-triple-negative breast cancer (TNBC) effect in nude mice and documented its mechanism. We found that cordycepin reduced the volume and weight of MDA-MB-231 xenografts and affected the expression of proliferation-, apoptosis-, epithelial–mesenchymal transition-, and matrix metalloproteinase-related proteins without side effects. RNA sequencing screening, pathway enrichment, and the protein network interaction analysis revealed enriched pathways and targets mainly concentrated on the Hedgehog pathway and its core components of SHH and GLI2. This indicates that the Hedgehog pathway plays a central role in the cordycepin-mediated regulation of growth and metastasis formation in TNBC. The database analysis of the Hedgehog pathway markers (SHH, PTCH1, SMO, GLI1, and GLI2) revealed that the Hedgehog pathway is activated in breast cancer tissues, and its high expression is not conducive to a patient’s survival. Finally, we verified that cordycepin effectively inhibited the Hedgehog pathway in TNBC through Western blotting and immunohistochemistry. This study found that cordycepin could regulate the growth and metastasis formation of TNBC through the Hedgehog pathway in vivo, which provides new insights for targeting and treating breast cancer. MDPI 2022-09-08 /pmc/articles/PMC9499653/ /pubmed/36142286 http://dx.doi.org/10.3390/ijms231810362 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Wu, Wenya
Li, Xiaomin
Qi, Meng
Hu, Xin
Cao, Fenghua
Wu, Xiaoping
Fu, Junsheng
Cordycepin Inhibits Growth and Metastasis Formation of MDA-MB-231 Xenografts in Nude Mice by Modulating the Hedgehog Pathway
title Cordycepin Inhibits Growth and Metastasis Formation of MDA-MB-231 Xenografts in Nude Mice by Modulating the Hedgehog Pathway
title_full Cordycepin Inhibits Growth and Metastasis Formation of MDA-MB-231 Xenografts in Nude Mice by Modulating the Hedgehog Pathway
title_fullStr Cordycepin Inhibits Growth and Metastasis Formation of MDA-MB-231 Xenografts in Nude Mice by Modulating the Hedgehog Pathway
title_full_unstemmed Cordycepin Inhibits Growth and Metastasis Formation of MDA-MB-231 Xenografts in Nude Mice by Modulating the Hedgehog Pathway
title_short Cordycepin Inhibits Growth and Metastasis Formation of MDA-MB-231 Xenografts in Nude Mice by Modulating the Hedgehog Pathway
title_sort cordycepin inhibits growth and metastasis formation of mda-mb-231 xenografts in nude mice by modulating the hedgehog pathway
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9499653/
https://www.ncbi.nlm.nih.gov/pubmed/36142286
http://dx.doi.org/10.3390/ijms231810362
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