[Effect of RNAi-mediated STAT3 gene inhibition on metastasis of human pancreatic cancer cells].
OBJECTIVE
To investigate the effect of RNAi-mediated STAT3 gene inhibition on metastasis of human pancreatic cancer cells and its underlying mechanism.


METHODS
STAT3 shRNA expression vector was constructed and transfected into SW1990 cells. STAT3 mRNA and STAT3 DNA-binding activity were examined using reverse transcription polymerase chain reaction (RT-PCR) and electrophoretic mobility shift assay (EMSA), respectively. The metastasis ability of SW1990 cells in vivo was determined in acute hematogenous metastasis model using nude mice. RT-PCR was performed to detect the mRNA expression of the MMP-2 and VEGF.


RESULTS
The mRNA expression of STAT3 and STAT3 DNA-binding activity were inhibited significantly by stable transfection of STAT3 shRNA expressing vectors. RNAi inhibition of STAT3 significantly suppressed the metastasis ability of SW1990 cells in vivo, and also markedly reduced the mRNA expression of MMP-2 and VEGF in SW1990 cells.


CONCLUSIONS
Inhibition of STAT3 by RNAi significantly inhibits the metastasis ability of pancreatic cancer cells through down-regulation of MMP-2 and VEGF, and may provide a novel strategy for preventing the metastasis of pancreatic cancer.
Gao
Zhen
Z
Department of General Surgery, Affiliated First People's Hospital, Shanghai Jiaotong University, Shanghai 200080, China.
Huang
Chen
C
Qiu
Zheng-Jun
ZJ
Jiang
Tao
T
Zhu
Lin
L
Cao
Jun
J
Zhang
Fang
F
Huang
Ke-Jian
KJ
D000818:Animals; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D005822:Genetic Vectors; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics; D050796:STAT3 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D014162:Transfection; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
D012333:RNA, Messenger; D050796:STAT3 Transcription Factor; D042461:Vascular Endothelial Growth Factor A; D020778:Matrix Metalloproteinase 2