title: Sodium orthovanadate inhibits growth of human hepatocellular carcinoma cells in vitro and in an orthotopic model in vivo.
abstract: The transition metal vanadium is widely distributed in the environment and exhibits various biological and physiological effects in the human body. As a well known vanadium compound, sodium orthovanadate (SOV) has shown promising antineoplastic activity in several human cancers. However, the effects of SOV on liver cancer are still unknown. In this study, for the first time, we showed that SOV could effectively suppress proliferation, induce G2/M cell cycle arrest and apoptosis, and diminish the mitochondrial membrane potential (MMP) of HCC cells in vitro. In addition, our in vitro results were recapitulated in vivo, showing that SOV exhibited a dose-dependent inhibition of growth of human HCC in an orthotopic model, evidenced by the reduction in tumor size, proliferation index and microvessel density, and increase in cell apoptosis. Most important, we found that SOV could inhibit autophagy in HCC cells in vitro and in vivo, which plays a prodeath role. Thus, our findings suggest that SOV could effectively suppress the growth of human HCC through the regulations of proliferation, cell cycle, apoptosis and autophagy, and thus may act as a potential therapeutic agent in HCC treatment.
authors.affiliation: Key Laboratory of Hepatosplenic Surgery, Department of Hepatic Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China.
authors.forename: Yaohua
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Key Laboratory of Hepatosplenic Surgery, Department of Hepatic Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Department of Pediatric Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China.
authors.forename: Zhilin
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Key Laboratory of Hepatosplenic Surgery, Department of Hepatic Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China.
authors.forename: Dawei
authors.initials: D
authors.lastname: Wang
authors.affiliation: Key Laboratory of Hepatosplenic Surgery, Department of Hepatic Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China.
authors.forename: Baolei
authors.initials: B
authors.lastname: Zhao
authors.affiliation: Key Laboratory of Hepatosplenic Surgery, Department of Hepatic Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China.
authors.forename: Huayang
authors.initials: H
authors.lastname: Pan
authors.affiliation: Key Laboratory of Hepatosplenic Surgery, Department of Hepatic Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China.
authors.forename: Jizhou
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of General Surgery, The First Hospital of Harbin, Harbin 150001, China.
authors.forename: Dongsheng
authors.initials: D
authors.lastname: Xu
authors.affiliation: Key Laboratory of Hepatosplenic Surgery, Department of Hepatic Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China.
authors.forename: Xiaoyang
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Key Laboratory of Hepatosplenic Surgery, Department of Hepatic Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China.
authors.forename: Shangha
authors.initials: S
authors.lastname: Pan
authors.affiliation: Key Laboratory of Hepatosplenic Surgery, Department of Hepatic Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China.
authors.forename: Lianxin
authors.initials: L
authors.lastname: Liu
authors.affiliation: Key Laboratory of Hepatosplenic Surgery, Department of Hepatic Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China. Electronic address: hrbdwj@163.com.
authors.forename: Wenjie
authors.initials: W
authors.lastname: Dai
authors.affiliation: Key Laboratory of Hepatosplenic Surgery, Department of Hepatic Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China. Electronic address: jianghc2013@163.com.
authors.forename: Hongchi
authors.initials: H
authors.lastname: Jiang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D001343:Autophagy; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D059565:G2 Phase Cell Cycle Checkpoints; D056945:Hep G2 Cells; D006801:Humans; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D047368:Tumor Burden / Q000187:drug effects; D014638:Vanadates / Q000494:pharmacology*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D014638:Vanadates
keywords: Apoptosis; Autophagy; Growth; Hepatocellular carcinoma; Sodium orthovanadate