title: Huaier extract suppresses breast cancer via regulating tumor-associated macrophages.
abstract: 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.
authors.affiliation: Department of Breast Surgery, Qilu Hospital, Shandong University, School of Medicine, Wenhua West Road No. 107, Ji'nan, Shandong 250012, P. R. China.
authors.forename: Yaming
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Breast Surgery, Qilu Hospital, Shandong University, School of Medicine, Wenhua West Road No. 107, Ji'nan, Shandong 250012, P. R. China.
authors.forename: Wenwen
authors.initials: W
authors.lastname: Qi
authors.affiliation: Department of Breast Surgery, Qilu Hospital, Shandong University, School of Medicine, Wenhua West Road No. 107, Ji'nan, Shandong 250012, P. R. China.
authors.forename: Xiaojin
authors.initials: X
authors.lastname: Song
authors.affiliation: Department of Breast Surgery, Qilu Hospital, Shandong University, School of Medicine, Wenhua West Road No. 107, Ji'nan, Shandong 250012, P. R. China.
authors.forename: Shangge
authors.initials: S
authors.lastname: Lv
authors.affiliation: Department of Breast Surgery, Qilu Hospital, Shandong University, School of Medicine, Wenhua West Road No. 107, Ji'nan, Shandong 250012, P. R. China.
authors.forename: Hanwen
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Breast Surgery, Qilu Hospital, Shandong University, School of Medicine, Wenhua West Road No. 107, Ji'nan, Shandong 250012, P. R. China.|Department of Radiation Oncology, UMDNJ-Robert Wood Johnson School of Medicine, and the Cancer Institute of New Jersey, New Brunswick, NJ, U.S.A.
authors.forename: Qifeng
authors.initials: Q
authors.lastname: Yang
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D045424:Complex Mixtures / Q000737:chemistry / Q000494:pharmacology*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D008264:Macrophages / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D055454:Trametes / Q000737:chemistry*; D059016:Tumor Microenvironment / Q000187:drug effects*
chemical_list: D045424:Complex Mixtures
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