title: A Huaier polysaccharide restrains hepatocellular carcinoma growth and metastasis by suppression angiogenesis.
abstract: Hepatocellular carcinoma (HCC) is a highly metastatic cancer. Huaier polysaccharide (TP-1) is a naturally occurring bioactive macromolecule, found in Huaier fungus and has been shown to exert in vitro antitumor and antimetastasis for HCC, but no study has addressed in vivo efficacy and mechanisms of action. Presently, we found that TP-1 at doses of 0.5, 1 and 2mg/kg significantly inhibited tumor growth and metastasis to the lung in mice bearing HCC SMMC-7721 tumors without toxicity. The analysis of tumors by immunohistochemistry demonstrated that TP-1 inhibited PCNA expression, increased the number of TUNEL-positive cells and reduced microvessel density (MVD) to achieve this effect. Furthermore, TP-1 administration reduced the protein expression of hypoxia-inducible factor (HIF)-1alpha, vascular endothelial growth factor (VEGF), AUF-1 and AEG-1, in tumor tissues. Taken together, our data suggested that the antitumor and anti-metastatic activities of TP-1 might be at least partially through down-regulation of HIF-1alpha/VEGF and AUF-1/AEG-1 signaling pathways.
authors.affiliation: Intervention Therapy Center of Liver Diseases, Beijing You An Hospital, Capital Medical University, Beijing 100069, China.
authors.forename: Cong
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Infectious Disease, the Second Affiliated Hospital of Harbin Medical University, Huanghe Road, Harbin 150081, China. Electronic address: hepato_wuxia@126.com.
authors.forename: Xia
authors.initials: X
authors.lastname: Wu
authors.affiliation: Intervention Therapy Center of Liver Diseases, Beijing You An Hospital, Capital Medical University, Beijing 100069, China.
authors.forename: Honghai
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Intervention Therapy Center of Liver Diseases, Beijing You An Hospital, Capital Medical University, Beijing 100069, China.
authors.forename: Gengxia
authors.initials: G
authors.lastname: Yang
authors.affiliation: Intervention Therapy Center of Liver Diseases, Beijing You An Hospital, Capital Medical University, Beijing 100069, China.
authors.forename: Meijun
authors.initials: M
authors.lastname: Hao
authors.affiliation: Intervention Therapy Center of Liver Diseases, Beijing You An Hospital, Capital Medical University, Beijing 100069, China.
authors.forename: Shoupeng
authors.initials: S
authors.lastname: Sheng
authors.affiliation: Intervention Therapy Center of Liver Diseases, Beijing You An Hospital, Capital Medical University, Beijing 100069, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Intervention Therapy Center of Liver Diseases, Beijing You An Hospital, Capital Medical University, Beijing 100069, China.
authors.forename: Jiang
authors.initials: J
authors.lastname: Long
authors.affiliation: Intervention Therapy Center of Liver Diseases, Beijing You An Hospital, Capital Medical University, Beijing 100069, China.
authors.forename: Caixia
authors.initials: C
authors.lastname: Hu
authors.affiliation: School of Medicine, Tsinghua Center for Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Xicai
authors.initials: X
authors.lastname: Sun
authors.affiliation: Institute of Liver Diseases, Beijing You An Hospital, Capital Medical University, Beijing 100069, China.
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.affiliation: Intervention Therapy Center of Liver Diseases, Beijing You An Hospital, Capital Medical University, Beijing 100069, China. Electronic address: jiashengzheng@outlook.com.
authors.forename: Jiasheng
authors.initials: J
authors.lastname: Zheng
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000473:pathology; D015815:Cell Adhesion Molecules / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D000081035:Heterogeneous Nuclear Ribonucleoprotein D0; D034502:Heterogeneous-Nuclear Ribonucleoprotein D / Q000378:metabolism; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008175:Lung Neoplasms / Q000188:drug therapy / Q000556:secondary*; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D055806:Microvessels / Q000187:drug effects / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000473:pathology; D011134:Polysaccharides / Q000494:pharmacology / Q000627:therapeutic use*; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D047368:Tumor Burden / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D015815:Cell Adhesion Molecules; C000630986:HNRNPD protein, human; D000081035:Heterogeneous Nuclear Ribonucleoprotein D0; D034502:Heterogeneous-Nuclear Ribonucleoprotein D; C000630987:Hnrpd protein, mouse; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D011134:Polysaccharides; D018809:Proliferating Cell Nuclear Antigen; D042461:Vascular Endothelial Growth Factor A
keywords: Angiogenesis; Huaier polysaccharide; Metastasis