title: RNAi-mediated inhibition of Raf-1 leads to decreased angiogenesis and tumor growth in gastric cancer.
abstract: Tumor angiogenesis plays an important role in the malignancy of solid tumors. A number of recent studies including our own have suggested that Raf-1 is involved in this process, and may be critical in regulating gene activation of several angiogenesis factors. RNA interference (RNAi) provides a powerful method for gene silencing in eukaryotic cells, including proliferating mammalian cells. To further define Raf-1 function in angiogenesis and to explore novel approaches to modulate angiogenesis, we employed the small interference RNA technique to knockdown gene expression of Raf-1 in gastric cancer cells and observed the effect of silencing Raf-1 on gastric cancer tumorigenesis and angiogenesis in vitro and in nude mice. We found that the expression of double stranded RNA leads to the efficient and specific inhibition of endogenous Raf-1 protein expression in gastric cancer cell lines as determined by Western blotting. Raf-1 protein is a potential target for gastric cancer biological therapy. Inhibition of Raf-1 with siRNA technique could inhibit growth of the tumor graft and reduce angiogenesis in nude mice, which probably caused by downregulation of pro-angiogenesis molecules, such as VEGF and HIF-1alpha.Taken together, our findings indicate that specific Raf-1 targeting may have important therapeutic values for cancer therapy, and that individual Raf-1 may be a useful target in developing angiogenic inhibitors.
authors.affiliation: Department of Liver Transplantation Rehab, 302 Hospital of PLA, Beijing, China.
authors.forename: Fanping
authors.initials: F
authors.lastname: Meng
authors.forename: Baoxia
authors.initials: B
authors.lastname: Dong
authors.forename: Hanwei
authors.initials: H
authors.lastname: Li
authors.forename: Daiming
authors.initials: D
authors.lastname: Fan
authors.forename: Jie
authors.initials: J
authors.lastname: Ding
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D017077:Culture Media, Conditioned / Q000494:pharmacology; D019084:Fluorescent Antibody Technique, Indirect; D015972:Gene Expression Regulation, Neoplastic; D005822:Genetic Vectors; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000235:genetics* / Q000473:pathology; D019908:Proto-Oncogene Proteins c-raf / Q000235:genetics*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D013274:Stomach Neoplasms / Q000098:blood supply* / Q000235:genetics*; D014162:Transfection; D023041:Xenograft Model Antitumor Assays
chemical_list: D017077:Culture Media, Conditioned; D034741:RNA, Small Interfering; D019908:Proto-Oncogene Proteins c-raf