PMID- 17054436
OWN - NLM
STAT- MEDLINE
DCOM- 20061219
LR  - 20091119
IS  - 1347-9032 (Print)
IS  - 1347-9032 (Linking)
VI  - 97
IP  - 12
DP  - 2006 Dec
TI  - Inhibition of STAT3 activity with AG490 decreases the invasion of human 
      pancreatic cancer cells in vitro.
PG  - 1417-23
AB  - Signal transducer and activator of transcription 3 (STAT3) is a central 
      cytoplasmic transcription factor. Abnormal activation of STAT3 plays a critical 
      role in oncogenesis and has been found frequently in a wide variety of human 
      tumors including pancreatic cancer. In this study, we elucidated the significance 
      of the STAT3 signaling pathway on metastatic potentials of pancreatic cancer. We 
      found that phosphorylated STAT3 (p-STAT3) protein levels were significantly 
      higher in highly metastatic SW1990 cells compared to the poorly metastatic 
      CaPan-2 cells, which expressed weak levels of this protein. Furthermore, a Janus 
      kinase (JAK) specific inhibitor, AG490, significantly inhibited the expression of 
      p-STAT3, and subsequently reduced invasion and adhesion potential of SW1990 cells 
      compared to the cells treated with vehicle only. Finally, inhibition of the STAT3 
      signaling pathway by AG490 also led to a decrease in matrix metalloproteinase-2 
      and vascular endothelial growth factor expression at the protein and mRNA levels. 
      These results demonstrate that activation of the STAT3 signaling pathway plays an 
      important role in the progression of pancreatic cancer and that inhibition of 
      this pathway may be useful for an anti-invasive therapeutic option in pancreatic 
      cancer.
FAU - Huang, Chen
AU  - Huang C
AD  - Department of General Surgery, Affiliated First People's Hospital, Shanghai Jiao 
      Tong University, Shanghai 200080, China.
FAU - Cao, Jun
AU  - Cao J
FAU - Huang, Ke J
AU  - Huang KJ
FAU - Zhang, Fang
AU  - Zhang F
FAU - Jiang, Tao
AU  - Jiang T
FAU - Zhu, Lin
AU  - Zhu L
FAU - Qiu, Zheng J
AU  - Qiu ZJ
LA  - eng
PT  - Journal Article
DEP - 20061019
PL  - England
TA  - Cancer Sci
JT  - Cancer science
JID - 101168776
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (RNA, Messenger)
RN  - 0 (RNA, Neoplasm)
RN  - 0 (STAT3 Transcription Factor)
RN  - 0 (STAT3 protein, human)
RN  - 0 (Trans-Activators)
RN  - 0 (Tyrphostins)
RN  - 0 (VEGFA protein, human)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 0 (alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 3.4.24.24 (Matrix Metalloproteinase 2)
SB  - IM
MH  - Blotting, Western
MH  - Cell Adhesion/drug effects
MH  - Electrophoretic Mobility Shift Assay
MH  - Enzyme Inhibitors/*pharmacology
MH  - *Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Matrix Metalloproteinase 2/genetics/metabolism
MH  - Neoplasm Invasiveness/*prevention & control
MH  - Pancreatic Neoplasms/*drug therapy/enzymology/pathology
MH  - Phosphorylation/drug effects
MH  - Protein-Tyrosine Kinases/antagonists & inhibitors
MH  - RNA, Messenger/genetics/metabolism
MH  - RNA, Neoplasm/genetics/metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - STAT3 Transcription Factor/antagonists & inhibitors/genetics/*metabolism
MH  - Signal Transduction
MH  - Trans-Activators
MH  - Transcription, Genetic
MH  - Tumor Cells, Cultured
MH  - Tyrphostins/*pharmacology
MH  - Vascular Endothelial Growth Factor A/genetics/metabolism
EDAT- 2006/10/24 09:00
MHDA- 2006/12/21 09:00
CRDT- 2006/10/24 09:00
PHST- 2006/10/24 09:00 [pubmed]
PHST- 2006/12/21 09:00 [medline]
PHST- 2006/10/24 09:00 [entrez]
AID - CAS340 [pii]
AID - 10.1111/j.1349-7006.2006.00340.x [doi]
PST - ppublish
SO  - Cancer Sci. 2006 Dec;97(12):1417-23. doi: 10.1111/j.1349-7006.2006.00340.x. Epub 
      2006 Oct 19.