RNAi-mediated inhibition of Raf-1 leads to decreased angiogenesis and tumor growth in gastric cancer

• Published in: Cancer biology & therapy Vol. 8; no. 2; pp. 174 - 179
• Main Authors: Meng, Fanping, Dong, Baoxia, Li, Hanwei, Fan, Daiming, Ding, Jie
• Format: Journal Article
• Language: English
• Published: United States Taylor & Francis 01.01.2009
• Subjects: Animals; Binding; Biology; Bioscience; Calcium; Cancer; Cell; Cell Line, Tumor; Cell Proliferation - drug effects; Culture Media, Conditioned - pharmacology; Cycle; Fluorescent Antibody Technique, Indirect; Gene Expression Regulation, Neoplastic; Genetic Vectors; Humans; Immunohistochemistry; Landes; Mice; Mice, Nude; Neovascularization, Pathologic - genetics; Neovascularization, Pathologic - pathology; Organogenesis; Proteins; Proto-Oncogene Proteins c-raf - genetics; RNA Interference; RNA, Small Interfering - metabolism; Stomach Neoplasms - blood supply; Stomach Neoplasms - genetics; Transfection; Xenograft Model Antitumor Assays
• ISSN: 1538-4047; 1555-8576
• DOI: 10.4161/cbt.8.2.7208

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 down regulation of pro-angiogenesis molecules, such as VEGF and HIF-1α.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.