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-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. ©2009 Landes Bioscience.