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Triplex-forming oligodeoxynucleotides targeting survivin inhibit proliferation and induce apoptosis of human lung carcinoma cells

Cancer Gene Therapy volume 10, pages 403–410 (2003)Cite this article

Abstract

Survivin is expressed in most cancers but is undetectable in differentiated adult cells, and plays an important role both in the suppression of apoptosis and mitotic spindle checkpoint; thus it has attracted great interest as a potential drug target. In this study, we investigated the antigene and antiproliferative effects of triplex-forming oligodeoxynucleotides (TFO) targeting survivin in human lung carcinoma A549 cells. Survivin-specific TFOs form stable triplexes under physiological conditions as tested by electrophoretic mobility shift assays. Treatment of A549 cells with survivin-specific but not control TFOs at a concentration of 400 nM in the presence of uptake-enhancing liposome significantly reduced survivin protein level, inhibited cell proliferation, and induced cell apoptosis as demonstrated by immunoblot, cell number counting, and Annexin V-staining. Moreover, we found that the triplex-forming potential of TFOs measured in vitro does not necessarily correlate with the ability of TFOs to affect expression of a targeted gene in vivo. Our results indicate that targeting survivin is a promising alternative strategy for the development of novel anticancer therapeutics.

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Acknowledgements

We thank Stephen Meier for technical assistance. This work is supported by German BMBF grant and IZKF_C10, University of Ulm.

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Authors and Affiliations

  1. Department of Nuclear Medicine, University of Ulm, Ulm, Germany

    Changxian Shen, Andreas Buck, Bülent Polat, Christiane Matuschek & Sven N Reske

  2. Department of Clinical Chemistry, University of Ulm, Ulm, Germany

    Alexandra Schmid-Kotsas, Hans-Juergen Gross & Max Bachem

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  1. Changxian Shen
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Correspondence to Sven N Reske.

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Shen, C., Buck, A., Polat, B. et al. Triplex-forming oligodeoxynucleotides targeting survivin inhibit proliferation and induce apoptosis of human lung carcinoma cells. Cancer Gene Ther 10, 403–410 (2003). https://doi.org/10.1038/sj.cgt.7700581

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