RNA interference‐mediated signal transducers and activators of transcription 3 gene silencing inhibits invasion and metastasis of human pancreatic cancer cells

• Published in: Cancer science Vol. 98; no. 7; pp. 1099 - 1106
• Main Authors: Qiu, Zhengjun, Huang, Chen, Sun, Jing, Qiu, Wei, Zhang, Jufeng, Li, Huiming, Jiang, Tao, Huang, Kejian, Cao, Jun
• Format: Journal Article
• Language: English
• Published: Melbourne, Australia Blackwell Publishing Asia 01.07.2007; Blackwell
• Subjects: Biological and medical sciences; Cell Division; DNA Primers; Gastroenterology. Liver. Pancreas. Abdomen; Gene Silencing; Humans; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Medical sciences; Neoplasm Invasiveness - genetics; Neoplasm Metastasis - genetics; Original; Pancreatic Neoplasms - genetics; Reverse Transcriptase Polymerase Chain Reaction; RNA Interference - physiology; STAT3 Transcription Factor - genetics; Tumors; Human; RNA interference; Metastasis; Malignant tumor; Invasion; Gene silencing; Cancerology; Pancreas cancer; Digestive diseases; Inhibitor; Transduction factor STAT; Tumor cell; Pancreatic disease
• ISSN: 1347-9032; 1349-7006
• DOI: 10.1111/j.1349-7006.2007.00485.x

Signal transducers and activators of transcription‐3 (STAT3), a central cytoplasmic transcription factor, is frequently overexpressed and constitutively activated by tyrosine during malignant transformation. The overexpression and phosphorylation of STAT3 in pancreatic cancer has been described only recently, but the roles and mechanism still remain unclear. In this study, we elucidate the significance of the STAT3 signaling pathway in metastatic potentials of pancreatic cancer. We stably silence the expression of the STAT3 and p‐STAT3 by using RNA interference (RNAi) in the pancreatic cancer cell line SW1990, and then reduce its invasion capacity in vitro and metastasis capacity in vivo compared to parental cells or cells tansfected with a control vector. Furthermore, silencing SW1990 cells with the STAT3 gene by RNAi also led to a decrease of matrix metalloproteinases‐2 (MMP‐2) and vascular endothelial growth factor (VEGF) at the mRNA and protein level. Collectively, these studies suggest that activation of the STAT3 signaling pathway plays an important role in the progression of pancreatic cancer, and that silence of the STAT3 gene with RNAi may be a useful anti‐invasive therapeutic option in pancreatic cancer. (Cancer Sci 2007; 98: 1099–1106)