title: Knockdown of S100A4 chemosensitizes human laryngeal carcinoma cells in vitro through inhibition of Slug.
abstract: OBJECTIVE
  S100A4 and Slug are known to be closely involved in resistance to chemotherapy. Furthermore, Slug signal was regulated by S100A4. Targeted therapy reducing S100A4 expression and Slug pathway activity may overcome the chemoresistance of human cancers. We hypothesized that over-expression of S100A4 and Slug was associated with the resistance to cisplatin of laryngeal carcinoma Hep-2 cells. We explored whether S100A4 silencing inhibited Slug, resulting in sensitization of laryngeal carcinoma Hep-2 cells to cisplatin.
  
  
  METHODS
  We investigated the effects of S100A4 and Slug silencing by siRNA transfection on chemosensitivity to cisplatin (DDP) in Hep-2 cells in vitro. In order to confirm the correlation between S100A4 and Slug signals, siRNA transfected Hep-2 cells were over-expressed by pSlug transfection, then explored the effect of S100A4 silencing on chemosensitivity to cisplatin (DDP) in Hep-2 cells in vitro. Real-time RT-PCR and Western blotting confirmed the presence of S100A4 mRNA, Slug mRNA and proteins in Hep-2 cells.
  
  
  RESULTS
  We found that resistance or insensitivity of Hep-2 cells to cisplatin might be associated with S100A4 and Slug expression. Knockdown of S100A4 and Slug markedly enhanced the cisplatin-induced suppression of Hep-2 cell growth and increased apoptosis. Knockdown of S100A4 may significantly reduce the levels of S100A4 mRNA, Slug mRNA and proteins, in cisplatin-treated Hep-2 cells. Re-expression of Slug in S100A4 siRNA transfected Hep-2 cells restored the cisplatin resistance in the Hep-2 cells.
  
  
  CONCLUSIONS
  Overexpression of S100A4 may be associated with the resistance to cisplatin of laryngeal carcinoma Hep-2 cells. Knockdown of S100A4 enhances the sensitivity to cisplatin of laryngeal carcinoma cells via inhibition of Slug expression.
authors.affiliation: Otolaryngology, the Affiliated Hospital of Qingdao University, Qingdao, China. chenzhijun2014715@126.com.
authors.forename: D-P
authors.initials: DP
authors.lastname: Liang
authors.forename: T-Q
authors.initials: TQ
authors.lastname: Huang
authors.forename: S-J
authors.initials: SJ
authors.lastname: Li
authors.forename: Z-J
authors.initials: ZJ
authors.lastname: Chen
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D055785:Gene Knockdown Techniques / Q000379:methods; D006801:Humans; D007822:Laryngeal Neoplasms / Q000378:metabolism* / Q000473:pathology; D034741:RNA, Small Interfering / Q000235:genetics; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins / Q000096:biosynthesis* / Q000172:deficiency / Q000235:genetics; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000037:antagonists & inhibitors* / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D034741:RNA, Small Interfering; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins; C000604407:SNAI1 protein, human; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; C077591:S100A4 protein, human; D002945:Cisplatin