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Small interfering RNA targeting Raf-1 inhibits tumor growth in vitro and in vivo

Cancer Gene Therapy volume 12, pages 682–690 (2005)Cite this article

Abstract

Raf-1 is a cytosolic serine-threonine kinase that plays an important role in tumor cell growth, proliferation, and apoptosis. Upregulated Raf-1 activity has also been implicated in tumor angiogenesis and metastasis. In this study, we used a promising new RNA interfering technology that targets Raf-1 mRNA both in vitro and in vivo. We initially found that Raf-1 siRNA markedly reduced Raf-1 mRNA in MDA-MB-435 cells in vitro by approximately 75% compared to control siRNA treatment groups. Raf-1 siRNA also reduced cell number by inducing apoptosis in a number of cell lines including HUVEC, MDA-MB-435, and C6 cells. After screening several histidine–lysine polymers in complex with Raf-1 siRNA to reduce tumor growth, we further evaluated the efficacy of this siRNA in complex with the optimal histidine–lysine carrier to reduce the tumor growth in vivo. MDA-MB-435 xenografts treated by intratumoral injections of Raf-1 siRNA were significantly reduced compared with the control groups. By the fourth measurement, tumor growth was reduced by nearly 60% in the Raf-1 siRNA treatment group compared with the untreated group (P<.02). Taken together, our data provide evidence that Raf-1 siRNA may be an effective strategy for reducing tumor growth.

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Acknowledgements

We thank Dr. Pamela Talalay for her careful reading and helpful suggestions of this manuscrift. This work was supported by the National Institutes of Health (CA101466).

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  1. Department of Pathology, University of Maryland Baltimore, MSTF Building, 10 South Pine Street, Baltimore, 21201, Maryland, USA

    Qixin Leng & Archibald James Mixson

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  1. Qixin Leng
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  2. Archibald James Mixson
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Correspondence to Archibald James Mixson.

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Leng, Q., Mixson, A. Small interfering RNA targeting Raf-1 inhibits tumor growth in vitro and in vivo. Cancer Gene Ther 12, 682–690 (2005). https://doi.org/10.1038/sj.cgt.7700831

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