title: Arsenic trioxide: marked suppression of tumor metastasis potential by inhibiting the transcription factor Twist in vivo and in vitro.
abstract: OBJECTIVE
  Arsenic trioxide (ATO) has been found effective in several types of cancer cells, including acute promyelocytic leukemia, and recently in hepatocellular carcinoma (HCC). In this study, we investigated the role of ATO in regulating the invasive activity of HCC after transarterial embolization (TAE).
  
  
  METHODS
  Cell migration and invasion were observed using Transwell and wound-healing assay. The molecular changes in E-cadherin, N-cadherin, and Vimentin of surviving tumor cells were determined by Western blotting. The effects of ATO on Twist activity of the tumor cells were further analyzed. In animal study, 40 male buffalo rats implanted with McA-RH7777 tumor in the liver were randomly divided into four groups: control, TAE, ATO, and TAE + ATO. TAE procedures were performed on the 14th day after implantation. Lung metastases were observed using fluorescence imaging, and the molecular changes in residual tumor cells were evaluated by Western blotting or immunohistochemistry. Tumor growth and survival analysis were also evaluated.
  
  
  RESULTS
  Arsenic trioxide markedly reduced cell migration and invasiveness, which were enhanced by hypoxia after TAE. Western blot analysis revealed ATO inhibited the expression of epithelial-mesenchymal transition (EMT) markers by suppressing Twist. The marked suppression effect of ATO on invasiveness and metastatic potential related to EMT was also shown in tissue.
  
  
  CONCLUSIONS
  The results of this study demonstrated that ATO is an effective anticancer agent in combination with TAE in the treatment of HCC, by suppressing tumor progression and metastasis via selectively inducing tumor cell apoptosis and arresting EMT by inhibiting the Twist activation.
authors.affiliation: Department of Intervention Radiology, Zhongshan Hospital Fudan University, No. 180 Fenglin Road, Xuhui, Shanghai, China.
authors.forename: Guang-Zhi
authors.initials: GZ
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Zhu-Ting
authors.initials: ZT
authors.lastname: Fang
authors.forename: Wen
authors.initials: W
authors.lastname: Zhang
authors.forename: Min-Jie
authors.initials: MJ
authors.lastname: Yang
authors.forename: Guo-Wei
authors.initials: GW
authors.lastname: Yang
authors.forename: Shuo
authors.initials: S
authors.lastname: Li
authors.forename: Lian
authors.initials: L
authors.lastname: Zhu
authors.forename: Li-Li
authors.initials: LL
authors.lastname: Wang
authors.forename: Wei-Sheng
authors.initials: WS
authors.lastname: Zhang
authors.forename: Rong
authors.initials: R
authors.lastname: Liu
authors.forename: Sheng
authors.initials: S
authors.lastname: Qian
authors.forename: Jian-Hua
authors.initials: JH
authors.lastname: Wang
authors.forename: Xu-Dong
authors.initials: XD
authors.lastname: Qu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000556:secondary; D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D004621:Embolization, Therapeutic / Q000009:adverse effects*; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008175:Lung Neoplasms / Q000517:prevention & control* / Q000556:secondary; D008297:Male; D009362:Neoplasm Metastasis; D010087:Oxides / Q000627:therapeutic use*; D051381:Rats; D011915:Rats, Inbred BUF; D051879:Twist-Related Protein 1 / Q000037:antagonists & inhibitors*
chemical_list: D000970:Antineoplastic Agents; D001152:Arsenicals; D010087:Oxides; D051879:Twist-Related Protein 1; D000077237:Arsenic Trioxide
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