title: Suppression of STAT3 by chemically modified siRNAs increases the chemotherapeutic sensitivity of parental and cisplatin-resistant non-small cell lung cancer cells.
abstract: OBJECTIVE
  Increased activation of the JAK-STAT signaling pathway is frequently observed in several primary cancers as well as cancer cell lines. Thus, targeting JAK-STAT pathway components by different molecular-biologic approaches in the search for new anticancer therapies has become widespread and resulted in encouraging outcomes. In this study, the effects of chemically modified anti-STAT3 small interfering (si)RNAs on cell viability, proliferation and apoptosis of parental and cisplatin resistant non-small cell lung cancer (NSCLC) cells were investigated with the aim to provide a new therapeutic strategy for overcoming cisplatin resistance in lung cancer.
  
  
  METHODS
  The parental NSCLC cell line Calu1 and its cisplatin- resistant subline CR-Calu1 were used to study the effects of STAT3 suppression with chemically modified anti-STAT3 siRNAs. STAT3 gene and protein expressions were analyzed by real-time (RT) quantitative (q) PCR and Western blot, respectively. Apoptosis was evaluated by Caspase-3 activity and cell death assays.
  
  
  RESULTS
  STAT3 messenger (m)RNA and protein expression were significantly increased in CR-Calu1 cells and suppressing its expression with specific siRNAs increased the rate of apoptosis through Caspase-3 activation. STAT3 suppression also significantly increased cisplatin sensitivity of Calu1 and CR-Calu1 cells after transfection with STAT3 siRNAs.
  
  
  CONCLUSIONS
  NSCLC cells could be sensitized to cisplatin by targeting STAT3 with chemically modified siRNAs together, a fact which was accompanied with increased apoptosis.
authors.affiliation: Department of Medical Biology, Ege University School of Medicine, Izmir, Turkey.
authors.forename: Burcinn
authors.initials: B
authors.lastname: Tezcanli Kaymaz
authors.forename: Vildan
authors.initials: V
authors.lastname: Bozok Cetintas
authors.forename: Zuhal
authors.initials: Z
authors.lastname: Eroglu
authors.forename: Buket
authors.initials: B
authors.lastname: Kosova
mesh_terms: D017209:Apoptosis; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival; D002945:Cisplatin / Q000008:administration & dosage; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D006801:Humans; D034741:RNA, Small Interfering / Q000737:chemistry / Q000235:genetics*; D050796:STAT3 Transcription Factor / Q000235:genetics* / Q000378:metabolism
chemical_list: D034741:RNA, Small Interfering; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D002945:Cisplatin