title: STAT3 oligonucleotide inhibits tumor angiogenesis in preclinical models of squamous cell carcinoma.
abstract: OBJECTIVE
  Signal transducer and activator of transcription 3 (STAT3) has shown to play a critical role in head and neck squamous cell carcinoma (HNSCC) and we have recently completed clinical trials of STAT3 decoy oligonucleotide in patients with recurrent or metastatic HNSCC. However, there is limited understanding of the role of STAT3 in modulating other aspects of tumorigenesis such as angiogenesis. In this study, we aimed to examine the effects of STAT3 decoy oligonucleotide on tumor angiogenesis.
  
  
  METHODS
  A STAT3 decoy oligonucleotide and small interfering RNA (siRNA) were used to inhibit STAT3 in endothelial cells in vitro and in vivo. The biochemical effects of STAT3 inhibition were examined in conjunction with the consequences on proliferation, migration, apoptotic staining, and tubule formation. Additionally, we assessed the effects of STAT3 inhibition on tumor angiogenesis using murine xenograft models.
  
  
  RESULTS
  STAT3 decoy oligonucleotide decreased proliferation, induces apoptosis, decreased migration, and decreased tubule formation of endothelial cells in vitro. The STAT3 decoy oligonucleotide also inhibited tumor angiogenesis in murine tumor xenografts. Lastly, our data suggest that the antiangiogenic effects of STAT3 decoy oligonucleotide were mediatedthrough the inhibition of both STAT3 and STAT1.
  
  
  CONCLUSIONS
  The STAT3 decoy oligonucleotidewas found to be an effective antiangiogenic agent, which is likely to contribute to the overall antitumor effects of this agent in solid tumors.Taken together with the previously demonstrated antitumor activity of this agent, STAT3 decoy oligonucleotide represents a promising single agent approach to targeting both the tumor and vascular compartments in various malignancies.
authors.affiliation: Department of Otolaryngology, School of Medicine, University of Pittsburgh, Pennsylvania, United States of America.
authors.forename: Jonah D
authors.initials: JD
authors.lastname: Klein
authors.affiliation: Department of Biology and Function in Head and Neck, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Sano
authors.affiliation: Department of Otolaryngology, School of Medicine, University of Pittsburgh, Pennsylvania, United States of America.
authors.forename: Malabika
authors.initials: M
authors.lastname: Sen
authors.affiliation: Department of Head and Neck Surgery, University of Texas M.D. Anderson Cancer Center, Texas, United States of America.
authors.forename: Jeffrey N
authors.initials: JN
authors.lastname: Myers
authors.affiliation: Department of Otolaryngology, School of Medicine, University of Pittsburgh, Pennsylvania, United States of America ; Department of Pharmacology and Chemical Biology, School of Medicine, University of Pittsburgh, Pennsylvania, United States of America.
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Grandis
authors.affiliation: Department of Otolaryngology, School of Medicine, University of Pittsburgh, Pennsylvania, United States of America ; Department of Pharmacology and Chemical Biology, School of Medicine, University of Pittsburgh, Pennsylvania, United States of America.
authors.forename: Seungwon
authors.initials: S
authors.lastname: Kim
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology*; D002460:Cell Line; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D002470:Cell Survival / Q000235:genetics; D004195:Disease Models, Animal; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000473:pathology*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D009389:Neovascularization, Pathologic / Q000235:genetics*; D009841:Oligonucleotides / Q000008:administration & dosage*; D050794:STAT1 Transcription Factor / Q000037:antagonists & inhibitors / Q000235:genetics; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors / Q000235:genetics*; D000077195:Squamous Cell Carcinoma of Head and Neck; D023041:Xenograft Model Antitumor Assays
chemical_list: D009841:Oligonucleotides; D050794:STAT1 Transcription Factor; D050796:STAT3 Transcription Factor