title: STAT3-targeting RNA interference inhibits pancreatic cancer angiogenesis in vitro and in vivo.
abstract: Signal transducers and activators of transcription 3 (STAT3) is a central cytoplasmic transcription factor that is activated by phosphorylation in response to extracellular signals and oncogenes. STAT3 regulates a number of pathways important in tumorigenesis including cell cycle progression, apoptosis, tumor angiogenesis, invasion and metastasis, and tumor cell evasion of the immune system. Our studies demonstrated that constitutively activated STAT3 plays an important role in the angiogenesis of pancreatic cancer. The objective of this study was to evaluate the potential use of RNA interference (RNAi) to knock down the STAT3 gene and the effect on angiogenesis of human pancreatic cancer cells in vitro and in vivo. We stably inhibited the expression of STAT3 and phosphorylated STAT3 (p-STAT3) using RNAi in the SW1990 pancreatic cancer cell line. Furthermore, RNAi for STAT3 inhibited STAT3-induced HUVEC cell migration and cell proliferation, and significantly suppressed the levels of secreted vascular endothelial growth factor (VEGF) and matrix metalloproteinases-2 (MMP-2) of SW1990 cells. In vivo experiments showed that RNAi for STAT3 significantly suppressed tumor growth and angiogenesis of SW1990 cells. Furthermore, silencing the STAT3 gene in SW1990 cells by RNAi also led to a decrease of VEGF and MMP-2 at the mRNA and protein levels. Collectively, these results demonstrate that the STAT3 signaling pathway plays an important role in the angiogenesis of pancreatic cancer and that knockdown of the STAT3 gene using the RNAi technique may be a novel therapeutic option for the treatment of pancreatic cancer.
authors.affiliation: Department of General Surgery, Affiliated First People's Hospital, Shanghai Jiao Tong University, 200080 Shanghai, PR China.
authors.forename: Chen
authors.initials: C
authors.lastname: Huang
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
authors.forename: Jun
authors.initials: J
authors.lastname: Cao
authors.forename: Ke-Jian
authors.initials: KJ
authors.lastname: Huang
authors.forename: Zheng-Jun
authors.initials: ZJ
authors.lastname: Qiu
mesh_terms: D000818:Animals; D002453:Cell Cycle; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D002642:Chick Embryo; D042783:Endothelial Cells / Q000378:metabolism; D020868:Gene Silencing; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000473:pathology*; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D034741:RNA, Small Interfering; D050796:STAT3 Transcription Factor; D042461:Vascular Endothelial Growth Factor A; D020778:Matrix Metalloproteinase 2