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Huaier extract suppresses breast cancer via regulating tumor-associated macrophages

Macrophages in tumor microenvironment are mostly M2-polarized - and have been reported to promote tumorigenesis, which are also defined as tumor-associated macrophages (TAMs). Here, we examined the regulatory effects of Huaier extract on TAMs using RAW264.7 murine macrophage cell line. Our data demo...

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Autores principales: Li, Yaming, Qi, Wenwen, Song, Xiaojin, Lv, Shangge, Zhang, Hanwen, Yang, Qifeng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4735520/
https://www.ncbi.nlm.nih.gov/pubmed/26831282
http://dx.doi.org/10.1038/srep20049
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author Li, Yaming
Qi, Wenwen
Song, Xiaojin
Lv, Shangge
Zhang, Hanwen
Yang, Qifeng
author_facet Li, Yaming
Qi, Wenwen
Song, Xiaojin
Lv, Shangge
Zhang, Hanwen
Yang, Qifeng
author_sort Li, Yaming
collection PubMed
description Macrophages in tumor microenvironment are mostly M2-polarized - and have been reported to promote tumorigenesis, which are also defined as tumor-associated macrophages (TAMs). Here, we examined the regulatory effects of Huaier extract on TAMs using RAW264.7 murine macrophage cell line. Our data demonstrated that Huaier extract could inhibit the infiltration of macrophages into tumor microenvironment in a dose-dependent manner. By performing RT-PCR, immunofluorescence and phagocytosis assay, we were able to find that Huaier extract could regulate the polarization of macrophages, with decreased M2-polarization and increased phagocytosis of RAW264.7 cells. Moreover, we identified that Huaier extract could suppress macrophages-induced angiogenesis by using HUVEC migration assay, tube formation and chorioallantoic membrane assay. Additionally, western blotting showed decreased expression of MMP2, MMP9 and VEGF with the use of Huaier extract. Finally, we found that Huaier extract could inhibit M2-macrophages infiltration and angiogenesis through treating 4T1 tumor bearing mice with Huaier extract. Our study revealed a novel mechanism of the anti-tumor effect of Huaier extract which inhibited angiogenesis by targeting TAMs. These findings provided that Huaier was a promising drug for clinical treatment of breast cancer.
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spelling pubmed-47355202016-02-05 Huaier extract suppresses breast cancer via regulating tumor-associated macrophages Li, Yaming Qi, Wenwen Song, Xiaojin Lv, Shangge Zhang, Hanwen Yang, Qifeng Sci Rep Article Macrophages in tumor microenvironment are mostly M2-polarized - and have been reported to promote tumorigenesis, which are also defined as tumor-associated macrophages (TAMs). Here, we examined the regulatory effects of Huaier extract on TAMs using RAW264.7 murine macrophage cell line. Our data demonstrated that Huaier extract could inhibit the infiltration of macrophages into tumor microenvironment in a dose-dependent manner. By performing RT-PCR, immunofluorescence and phagocytosis assay, we were able to find that Huaier extract could regulate the polarization of macrophages, with decreased M2-polarization and increased phagocytosis of RAW264.7 cells. Moreover, we identified that Huaier extract could suppress macrophages-induced angiogenesis by using HUVEC migration assay, tube formation and chorioallantoic membrane assay. Additionally, western blotting showed decreased expression of MMP2, MMP9 and VEGF with the use of Huaier extract. Finally, we found that Huaier extract could inhibit M2-macrophages infiltration and angiogenesis through treating 4T1 tumor bearing mice with Huaier extract. Our study revealed a novel mechanism of the anti-tumor effect of Huaier extract which inhibited angiogenesis by targeting TAMs. These findings provided that Huaier was a promising drug for clinical treatment of breast cancer. Nature Publishing Group 2016-02-01 /pmc/articles/PMC4735520/ /pubmed/26831282 http://dx.doi.org/10.1038/srep20049 Text en Copyright © 2016, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Li, Yaming
Qi, Wenwen
Song, Xiaojin
Lv, Shangge
Zhang, Hanwen
Yang, Qifeng
Huaier extract suppresses breast cancer via regulating tumor-associated macrophages
title Huaier extract suppresses breast cancer via regulating tumor-associated macrophages
title_full Huaier extract suppresses breast cancer via regulating tumor-associated macrophages
title_fullStr Huaier extract suppresses breast cancer via regulating tumor-associated macrophages
title_full_unstemmed Huaier extract suppresses breast cancer via regulating tumor-associated macrophages
title_short Huaier extract suppresses breast cancer via regulating tumor-associated macrophages
title_sort huaier extract suppresses breast cancer via regulating tumor-associated macrophages
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4735520/
https://www.ncbi.nlm.nih.gov/pubmed/26831282
http://dx.doi.org/10.1038/srep20049
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