title: [Inhibitory effect of AG490 on invasion and metastasis of human pancreatic cancer cells in vitro].
abstract: OBJECTIVE
  To investigate the effect and mechanism of blockade of STAT3 signaling pathway by JAK specific inhibitor-AG490 on invasion and metastasis of human highly metastatic pancreatic cancer line SW1990 in vitro.
  
  
  METHODS
  AG490 was added into the culture media for SW1990 cells. The invasion ability of SW1990 cells was determined by cell invasion assay kit. Western blot was performed to detect the protein expression of the STAT3, phosphorylated STAT3 (p-STAT3), MMP-2 and VEGF. RT-PCR was performed to detect the mRNA expression of the MMP-2 and VEGF.
  
  
  RESULTS
  20 micromol/L AG490 significantly inhibited the invasion ability of SW1990 cells and the inhibitory rate of invasion ability was (77.67 +/- 7.79) %. The use of AG490 not only markedly reduced the protein expression of p-STAT3, MMP-2 and VEGF, but also greatly reduced the mRNA expression of MMP-2 and VEGF.
  
  
  CONCLUSIONS
  Blocking STAT3 activation with AG490 can inhibit the invasion and metastasis ability of pancreatic cancer cells in vitro through down-regulation of MMP-2 and VEGF expression. Blocking STAT3 signaling pathway may provide a novel strategy in prevention of invasion and metastasis of pancreatic cancer.
authors.affiliation: Department of General Surgery, Affiliated First People's Hospital, Shanghai Jiao Tong University, Shanghai 200080, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Huang
authors.forename: Zheng-Jun
authors.initials: ZJ
authors.lastname: Qiu
authors.forename: Jun
authors.initials: J
authors.lastname: Cao
authors.forename: Ke-Jian
authors.initials: KJ
authors.lastname: Huang
authors.forename: Fang
authors.initials: F
authors.lastname: Zhang
authors.forename: Tao
authors.initials: T
authors.lastname: Jiang
authors.forename: Lin
authors.initials: L
authors.lastname: Zhu
authors.forename: Jun
authors.initials: J
authors.lastname: Liu
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D015153:Blotting, Western; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D053612:Janus Kinases / Q000037:antagonists & inhibitors; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation / Q000187:drug effects; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D020032:Tyrphostins / Q000494:pharmacology*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D012333:RNA, Messenger; D050796:STAT3 Transcription Factor; D020032:Tyrphostins; D042461:Vascular Endothelial Growth Factor A; C095512:alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide; D053612:Janus Kinases; D020778:Matrix Metalloproteinase 2