title: C60(OH)22: a potential histone deacetylase inhibitor with anti-angiogenic activity.
abstract: C60(OH)22has been reported to suppress human cancer by inhibiting angiogenesis. However, its mechanism of action remains unclear. To explore the role and mechanism of C60(OH)22in human pancreatic cancer, siRNA knockdown, immunofluorescence and a matrigel plug mouse model were employed. The results demonstrated that C60(OH)22suppresses endothelial cell invasion and tube formation in vitro. C60(OH)22suppresses angiogenesis in human umbilical vein endothelial cell (HUVEC) xenograft mice. The enzymatic activities of MMP2 and MMP9, as well as the expression levels of HDAC1, HDAC2, HIF-1α and VEGF, were inhibited by C60(OH)22. The expression of RECK was up-regulated by C60(OH)22in HUVECs. The expression levels of HIF-1α and VEGF were down-regulated and the expression of RECK was up-regulated after the knockdown of HDAC1 and HDAC2 in HUVECs. Cell invasion, tube formation, and the enzymatic activities of MMP2 and MMP9 were suppressed after the knockdown of HDAC1 or HDAC2 in HUVECs.
authors.affiliation: Department of Gastroenterology & Hepatology, Chinese PLA General Hospital, No. 28 Fuxing Road, Beijing 100853, China. mzguo@hotmail.com.
authors.forename: Chengdu
authors.initials: C
authors.lastname: Sun
authors.affiliation: Chinese Academy of Sciences Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology and Institute of High Energy Physics, No. 11, Beiyitiao Zhongguancun, Beijing 100190, China. chenchy@nanoctr.cn.
authors.forename: Liming
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology & Hepatology, Chinese PLA General Hospital, No. 28 Fuxing Road, Beijing 100853, China. mzguo@hotmail.com and Medical College of NanKai University, Tianjin, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Gao
authors.affiliation: Department of Gastroenterology & Hepatology, Chinese PLA General Hospital, No. 28 Fuxing Road, Beijing 100853, China. mzguo@hotmail.com and Chinese Academy of Sciences Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology and Institute of High Energy Physics, No. 11, Beiyitiao Zhongguancun, Beijing 100190, China. chenchy@nanoctr.cn.
authors.forename: Yuanming
authors.initials: Y
authors.lastname: Pan
authors.affiliation: Chinese Academy of Sciences Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology and Institute of High Energy Physics, No. 11, Beiyitiao Zhongguancun, Beijing 100190, China. chenchy@nanoctr.cn.
authors.forename: Yuliang
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Chinese Academy of Sciences Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology and Institute of High Energy Physics, No. 11, Beiyitiao Zhongguancun, Beijing 100190, China. chenchy@nanoctr.cn.
authors.forename: Chunying
authors.initials: C
authors.lastname: Chen
authors.affiliation: Department of Gastroenterology & Hepatology, Chinese PLA General Hospital, No. 28 Fuxing Road, Beijing 100853, China. mzguo@hotmail.com.
authors.forename: Mingzhou
authors.initials: M
authors.lastname: Guo
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D005260:Female; D037741:Fullerenes / Q000494:pharmacology*; D055785:Gene Knockdown Techniques; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D034741:RNA, Small Interfering; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; D037741:Fullerenes; C497442:HIF1A protein, human; D056572:Histone Deacetylase Inhibitors; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D034741:RNA, Small Interfering; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9; C069837:fullerene C60