Inhibition of gastric cancer angiogenesis by vector-based RNA interference for Raf-1.
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. To further define Raf-1 function in angiogenesis and to explore novel approaches to modulate angiogenesis, we employed the small interference RNA technique to knock-down gene expression of Raf-1 in gastric cancer cell line SGC7901 that expresses a high level of Raf-1. The protein level of Raf-1 in the SGC7901cells was decreased dramatically after transfection with a Raf-1 specific siRNA vector. Further study proved that, VEGF and HIF-1alpha, two angiogenesis promoting factors, were found to be downregulated. And we also find that Vector-based RNA interference for Raf-1 increases transfected gastric cell apoptosis and inhibits cellular proliferation. Our results suggest that Raf-1 may be involved in angiogenesis by controlling the expression of angiogenesis-related factors and provide a possible strategy for the treatment of tumor angiogenesis by targeting Raf-1.
Meng
Fanping
F
Institude of Digestive Disease, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi Province, PR, China.
Ding
Jie
J
Liu
Na
N
Zhang
Jing
J
Shao
Xiaodong
X
Shen
Huiqin
H
Xue
Yan
Y
Xie
Huahong
H
Fan
Daiming
D
D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D005822:Genetic Vectors; D006801:Humans; D009389:Neovascularization, Pathologic; D010957:Plasmids; D019908:Proto-Oncogene Proteins c-raf / Q000235:genetics* / Q000502:physiology*; D034622:RNA Interference; D013274:Stomach Neoplasms / Q000098:blood supply* / Q000235:genetics*; D015533:Transcriptional Activation; D014162:Transfection; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A / Q000502:physiology
D042461:Vascular Endothelial Growth Factor A; D019908:Proto-Oncogene Proteins c-raf