title: Plumbagin restrains hepatocellular carcinoma angiogenesis by suppressing the migration and invasion of tumor-derived vascular endothelial cells.
abstract: Tumor occurrence and development are very complicated processes. In addition to the roles of exogenous carcinogenic factors, the body's internal factors also play important roles. These factors include the host response to the tumor and the tumor effect on the host. In particular, the proliferation, migration and activation of endothelial cells are involved in tumor angiogenesis. Angiogenesis is one of the hallmarks of cancer. In this study, we investigate whether plumbagin can abrogate angiogenesis-mediated tumor growth in hepatocellular carcinoma (HCC) and, if so, through which molecular mechanisms. We observed that in co-cultures of the human endothelial cell line EA.hy926 and the human hepatoma cell line SMMC-7721 and Hep3B, the hepatoma cells induced migration, invasion, tube formation and viability of the EA.hy926 cells in vitro, and these processes were inhibited by plumbagin. Real-Time PCR, Western Blot and Immunofluorescence staining showed that plumbagin treatment suppressed expression of angiogenesis pathways (PI3K-Akt, VEGF/KDR and Angiopoietins/Tie2) and angiogenic factors (VEGF, CTGF, ET-1, bFGF),which is associated with tumor angiogenesis in cancer cells and xenograft tumor tissues. Furthermore, plumbagin was also found to significantly reduce tumor growth in an orthotopic HCC mouse model and to inhibit tumor-induced angiogenesis in HCC patient xenografts. Taken together, our findings strongly suggest that plumbagin might be a promising anti-angiogenic drug with significant antitumor activity in HCC.
authors.affiliation: Department of Physiology, Faculty of Basic Medicine, Guangxi University of Chinese Medicine, Nanning, Guangxi, 530200, China.
authors.forename: YanFei
authors.initials: Y
authors.lastname: Wei
authors.affiliation: Department of Emergency, Tianjin Fifth Central Hospital, Binhai New Area, Tianjin 300450, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Yang
authors.affiliation: Department of State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Nankai University, Tianjin, 710032, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Physiology, Faculty of Basic Medicine, Guangxi University of Chinese Medicine, Nanning, Guangxi, 530200, China.
authors.forename: TieJian
authors.initials: T
authors.lastname: Zhao
authors.affiliation: Department of Physiology, Faculty of Basic Medicine, Guangxi University of Chinese Medicine, Nanning, Guangxi, 530200, China.
authors.forename: XueMei
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Physiology, Faculty of Basic Medicine, Guangxi University of Chinese Medicine, Nanning, Guangxi, 530200, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhong
authors.affiliation: Department of Physiology, Faculty of Basic Medicine, Guangxi University of Chinese Medicine, Nanning, Guangxi, 530200, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Ma
authors.affiliation: Department of Physiology, Faculty of Basic Medicine, Guangxi University of Chinese Medicine, Nanning, Guangxi, 530200, China.
authors.forename: YongXin
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Physiology, Faculty of Basic Medicine, Guangxi University of Chinese Medicine, Nanning, Guangxi, 530200, China.
authors.forename: Chuan
authors.initials: C
authors.lastname: Zhao
authors.affiliation: Department of Physiology, Faculty of Basic Medicine, Guangxi University of Chinese Medicine, Nanning, Guangxi, 530200, China.
authors.forename: JunXuan
authors.initials: J
authors.lastname: Li
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D014408:Biomarkers, Tumor; D006528:Carcinoma, Hepatocellular / Q000098:blood supply / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000098:blood supply / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009285:Naphthoquinones / Q000494:pharmacology*; D009361:Neoplasm Invasiveness; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D020533:Angiogenesis Inhibitors; D000972:Antineoplastic Agents, Phytogenic; D014408:Biomarkers, Tumor; D009285:Naphthoquinones; D042461:Vascular Endothelial Growth Factor A; C014758:plumbagin
keywords: HCC; PI3K/AKT; angiogenesis; plumbagin; vascular endothelial cells