title: Periostin Contributes to Cisplatin Resistance in Human Non-Small Cell Lung Cancer A549 Cells via Activation of Stat3 and Akt and Upregulation of Survivin.
abstract: OBJECTIVE
  Periostin is upregulated in non-small cell lung cancer (NSCLC). This study was done to explore the function of periostin in the development of cisplatin (CDDP) resistance in NSCLC.
  
  
  METHODS
  The effects of overexpression or knockdown of periostin on CDDP sensitivity was examined in A549 cells. The involvement of signal transducer and activator of transcription 3 (Stat3) and Akt signaling in the action of periostin was checked. The in vivo effect of periostin silencing on CDDP susceptibility was determined in a mouse xenograft model.
  
  
  RESULTS
  Periostin was significantly upregulated in CDDP-resistant A549 cells, compared to parental controls. Overexpression of periostin rendered A549 cells more resistant to CDDP-induced apoptosis and enhanced Stat3 and Akt phosphorylation and survivin expression. Periostin-mediated protection against CDDP-induced apoptosis was compromised by downregulation of survivin. Furthermore, knockdown of periostin re-sensitized CDDP-resistant A549 cells to CDDP. After CDDP treatment, greater volume reduction was observed in periostin-silenced xenograft tumors than in control tumors, which was accompanied by reduced levels of phosphorylated Stat3 and survivin in periostin-depleted tumors.
  
  
  CONCLUSIONS
  In conclusion, periostin promotes CDDP resistance in NSCLC cells largely through activation of Stat3 and Akt and upregulation of survivin and thus represents a promising target for overcoming CDDP resistance.
authors.forename: Wenxia
authors.initials: W
authors.lastname: Hu
authors.forename: Pule
authors.initials: P
authors.lastname: Jin
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
mesh_terms: D000072283:A549 Cells; D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D002945:Cisplatin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009368:Neoplasm Transplantation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D000077022:Survivin
chemical_list: C107489:BIRC5 protein, human; D015815:Cell Adhesion Molecules; D051034:Inhibitor of Apoptosis Proteins; C512835:POSTN protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D000077022:Survivin; D051057:Proto-Oncogene Proteins c-akt; D002945:Cisplatin