title: [Sunitinib suppresses migration of ovarian cancer cells through negative modulation of TGF-β-mediated epithelial-mesenchymal transition].
abstract: To investigate the effect of sunitinib on the migration of ovarian cells and its mechanism of the negative regulation TGF-β mediated of epithelial-mesenchymal transition(EMT) by sunitinib to inhibit ovarian cancer metastasis.
  
  
  
  The migration of human ovarian cancer cells SKOV3 was evaluated by wound-healing and transwell assays. The effects of sunitinib on TGF-β-induced E-cadherin expression was assessed by Western-blotting, real time RT-PCR and immunofluorescence assay. The protein levels of Snail and the transcriptional activity of Smad in sunitinib-treated cells were examined by Western-blotting and SBE-luciferase assay.
  
  
  
  Sunitinib suppressed the migration of SKOV3 cells in a concentration-dependent manner. TGF-β stimulation reduced E-cadherin protein level, which was attenuated by sunitinib. Sunitinib inhibited the up-regulation of Snail protein level induced by TGF-β treatment. The SBE reporter was constructed by linking the Smad-binding elements promoter upstream of luciferase reporter gene. A remarkable increment of transcriptional activity of Smads complexes was observed in SKOV3 cells exposed to TGF-β, which was significantly prohibited by sunitinib.
  
  
  
  Sunitinib can inhibit the migration of SKOV3 cells and attenuate the down-regulation of E-cadherin protein level induced by TGF-β. Sunitinib can abolish TGF-β-induced up-regulation of Snail protein and decrease the transcriptional activity of Smad complexes. The results indicate that sunitinib suppresses migration of ovarian cancer cells through negative modulation of TGF-β-mediated epithelial-mesenchymal transition.
authors.affiliation: Zhejiang Provincial Key Laboratory of Anti-cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
authors.forename: Zi-bo
authors.initials: ZB
authors.lastname: Chen
authors.affiliation: Zhejiang Provincial Key Laboratory of Anti-cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
authors.forename: Lin-lin
authors.initials: LL
authors.lastname: Chang
authors.affiliation: Zhejiang Provincial Key Laboratory of Anti-cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
authors.forename: Tian-yi
authors.initials: TY
authors.lastname: Zhou
authors.affiliation: Zhejiang Provincial Key Laboratory of Anti-cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
authors.forename: Dan-dan
authors.initials: DD
authors.lastname: Wang
authors.affiliation: Zhejiang Provincial Key Laboratory of Anti-cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Yiwu Central Hospital, Yiwu 322000, China.
authors.forename: Ping-ge
authors.initials: PG
authors.lastname: Zhao
authors.affiliation: Zhejiang Provincial Key Laboratory of Anti-cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhu
mesh_terms: D015703:Antigens, CD; D015820:Cadherins / Q000378:metabolism; D045744:Cell Line, Tumor / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects*; D015536:Down-Regulation; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D010051:Ovarian Neoplasms / Q000473:pathology*; D011758:Pyrroles / Q000494:pharmacology*; D051785:Smad Proteins / Q000378:metabolism; D000071250:Snail Family Transcription Factors; D000077210:Sunitinib; D014157:Transcription Factors / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D015854:Up-Regulation
chemical_list: D015703:Antigens, CD; C513384:CDH1 protein, human; D015820:Cadherins; D007211:Indoles; D011758:Pyrroles; D051785:Smad Proteins; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D000077210:Sunitinib