gms | German Medical Science

61st Annual Meeting of the German Society of Neurosurgery (DGNC) as part of the Neurowoche 2010
Joint Meeting with the Brazilian Society of Neurosurgery on the 20 September 2010

German Society of Neurosurgery (DGNC)

21 - 25 September 2010, Mannheim

RNA interference targeting Survivin exerts anti-tumoral effects in vitro and in glioma xenografts

Meeting Abstract

  • Sandy Hendruschk - Klinik für Neurochirurgie, Universitätsklinikum Carl Gustav Carus der TU Dresden, Deutschland
  • Achim Aigner - Institut für Pharmakologie und Toxikologie, Universitätsklinikum Gießen und Marburg, Standort Marburg, Deutschland
  • Daniel Martin - Klinik für Neurochirurgie, Universitätsklinikum Carl Gustav Carus der TU Dresden, Deutschland
  • Matthias Kirsch - Klinik für Neurochirurgie, Universitätsklinikum Carl Gustav Carus der TU Dresden, Deutschland
  • Gabriele Schackert - Klinik für Neurochirurgie, Universitätsklinikum Carl Gustav Carus der TU Dresden, Deutschland
  • Achim Temme - Klinik für Neurochirurgie, Universitätsklinikum Carl Gustav Carus der TU Dresden, Deutschland

Deutsche Gesellschaft für Neurochirurgie. 61. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC) im Rahmen der Neurowoche 2010. Mannheim, 21.-25.09.2010. Düsseldorf: German Medical Science GMS Publishing House; 2010. DocP1717

DOI: 10.3205/10dgnc188, URN: urn:nbn:de:0183-10dgnc1884

Published: September 16, 2010

© 2010 Hendruschk et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en). You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.


Outline

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Objective: Despite multimodal treatments, the median survival of patients suffering from glioblastoma (GB) has not improved over the past decades. One promising approach to deal with GB is the inactivation of proteins essential for survival or progression by means of RNA interference (RNAi) techniques. A candidate for an RNAi therapy of gliomas is the inhibitor of apoptosis protein (IAP) survivin. Survivin is involved in two main cellular processes, cell division and inhibition of apoptosis. Since loss of survivin results in mitotic defects and cannot be compensated by other IAP familiy members such as XIAP or cIAP we sought to establish a survivin-RNAi-therapy of gliomas.

Methods: Knock down of survivin expression in glioma cells and xenografts was accomplished by retroviral shRNA vectors and polyethlyenimine-(PEI) complexed siRNA molecules, respectively. RNAi-effects were investigated by standard proliferation assays, measurement of tumor growth, QRT-PCR, and protein analyses, including proteome profiler blots.

Results: RNAi of survivin induced polyploidy and impaired proliferation of glioma cells. An upregulation of TRAIL and CD95/Fas was observed, making the glioma cells susceptible to NK cells. In vivo experiments using PEI-siRNA targeting survivin efficiently blocked subcutaneous U373 xenograft growth.

Conclusions: Survivin-RNAi is a promising strategy to impair glioma growth. Further experiments using immune-competent syngeneic mice are warranted to confirm the potential of this therapeutic approach.