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Published on: March 30, 2019
Inhibition of gastric cancer angiogenesis by vector-based RNA interference for Raf-1
Fanping Meng1, Jie Ding, Na Liu
1Institude of Digestive Disease, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi Province, PR, China.
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. 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.
Insights
Targeting Raf-1 kinase in gastric cancer cells inhibits tumor angiogenesis. Reducing Raf-1 levels suppressed key growth factors, increased cancer cell death, and slowed proliferation, offering a potential new treatment strategy.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Tumor angiogenesis is crucial for solid tumor growth and metastasis.
- Raf-1 kinase has been implicated in regulating genes that promote angiogenesis.
Purpose of the Study:
- To investigate the role of Raf-1 in gastric cancer angiogenesis.
- To explore targeting Raf-1 as a therapeutic strategy for tumor angiogenesis.
Main Methods:
- Utilized small interference RNA (siRNA) to reduce Raf-1 gene expression in SGC7901 gastric cancer cells.
- Quantified changes in Raf-1 protein levels, vascular endothelial growth factor (VEGF), and hypoxia-inducible factor-1 alpha (HIF-1alpha).
- Assessed effects on gastric cancer cell apoptosis and proliferation.
Main Results:
- Raf-1 specific siRNA significantly decreased Raf-1 protein levels in SGC7901 cells.
- Downregulation of Raf-1 led to reduced expression of VEGF and HIF-1alpha.
- Targeting Raf-1 increased apoptosis and inhibited proliferation in transfected gastric cancer cells.
Conclusions:
- Raf-1 plays a significant role in regulating angiogenesis by controlling key angiogenesis factors.
- Targeting Raf-1 represents a potential therapeutic approach for inhibiting tumor angiogenesis in gastric cancer.
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