RNAse A-like enzymes in serum inhibit the anti-neoplastic activity of siRNA targeting polo-like kinase 1
Article first published online: 9 MAR 2007
Copyright © 2007 Wiley-Liss, Inc.
International Journal of Cancer
Volume 121, Issue 1, pages 206–210, 1 July 2007
How to Cite
Haupenthal, J., Baehr, C., Zeuzem, S. and Piiper, A. (2007), RNAse A-like enzymes in serum inhibit the anti-neoplastic activity of siRNA targeting polo-like kinase 1. Int. J. Cancer, 121: 206–210. doi: 10.1002/ijc.22665
- Issue published online: 24 APR 2007
- Article first published online: 9 MAR 2007
- Manuscript Accepted: 23 JAN 2007
- Manuscript Received: 7 NOV 2006
- Wilhelm Sander-Stiftung. Grant Number: 2003.119.1
- Deutsche Forschungsgemeinschaft. Grant Number: Pi 258/7-4
- RNAse A
Down-modulation of target molecules in tumor cells by small interfering (si) RNAs is a promising anti-cancer strategy. A major challenge of this approach is the loss of silencing activity of the siRNAs in vivo. Our study aimed at investigating the influence of the serum compartment on the anti-tumor activity of siRNA directed against Polo-like kinase 1 (Plk1), a mitosis-associated serine/threonine kinase. The data showed that siRNA-induced suppression of Plk1 expression effectively reduced the viable cell mass and increased apoptosis in several cancer cell lines. Preincubation of the siRNA in human serum led to shortening of the siRNA as well as loss of its Plk1 silencing and anti-tumor activity. This loss of activity was prevented by inhibition of RNAse A-like enzymes. These data indicate that the anti-neoplastic effect of siRNAs declines upon incubation in human serum. This loss of anti-neoplastic activity can be prevented by inhibition of their degradation by RNAse A-like enzymes. This may have important implications for the development of a human therapeutic application of siRNAs. © 2007 Wiley-Liss, Inc.