Antisense-mediated inhibition of survivin, hTERT and VEGF in bladder cancer cells in vitro and in vivo

  • Authors:
    • Doreen Kunze
    • Daniela Wuttig
    • Ingo Kausch
    • Caroline Blietz
    • Lena Blumhoff
    • Yvonne Burmeister
    • Kai Kraemer
    • Susanne Fuessel
    • Marieta Toma
    • Bernd Schwenzer
    • Axel Meye
    • Marc-Oliver Grimm
    • Oliver W. Hakenberg
    • Dieter Jocham
    • Manfred P. Wirth
  • View Affiliations

  • Published online on: May 1, 2008     https://doi.org/10.3892/ijo.32.5.1049
  • Pages: 1049-1056
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Abstract

Since cancer cells are characterised by multiple genetic alterations the single inhibition of one tumour- associated gene might not be sufficient as a therapeutic strategy. We examined the effects of a combined inhibition of survivin, human telomerase reverse transcriptase (hTERT) and vascular endothelial growth factor (VEGF) with antisense oligodeoxynucleotides (AS-ODNs) and small interfering RNAs (siRNAs) in EJ28 and 5637 bladder cancer (BCa) cells. Following verification of the uptake of intraperitoneally applied fluorescence-labelled AS-ODNs and siRNAs in subcutaneous BCa xenografts, the target-directed constructs were tested as single agents in SCID mice bearing subcutaneous EJ28. Simultaneous inhibition of two of the selected transcripts significantly enhanced cell viability reduction compared to the controls consisting of a target directed construct and an appropriate control construct without any homology to the human genome. The uptake of both antisense inhibitor types in the subcutaneous BCa was achieved even without a carrier. In vivo studies with 9 consecutive intraperitoneal injections with 20 mg/kg AS-ODNs or 4.6 mg/kg siRNAs revealed the biocompatibility of both antisense inhibitor types and showed anti-tumoural activity of the AS-ODNs used.

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May 2008
Volume 32 Issue 5

Print ISSN: 1019-6439
Online ISSN:1791-2423

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APA
Kunze, D., Wuttig, D., Kausch, I., Blietz, C., Blumhoff, L., Burmeister, Y. ... Wirth, M.P. (2008). Antisense-mediated inhibition of survivin, hTERT and VEGF in bladder cancer cells in vitro and in vivo. International Journal of Oncology, 32, 1049-1056. https://doi.org/10.3892/ijo.32.5.1049
MLA
Kunze, D., Wuttig, D., Kausch, I., Blietz, C., Blumhoff, L., Burmeister, Y., Kraemer, K., Fuessel, S., Toma, M., Schwenzer, B., Meye, A., Grimm, M., Hakenberg, O. W., Jocham, D., Wirth, M. P."Antisense-mediated inhibition of survivin, hTERT and VEGF in bladder cancer cells in vitro and in vivo". International Journal of Oncology 32.5 (2008): 1049-1056.
Chicago
Kunze, D., Wuttig, D., Kausch, I., Blietz, C., Blumhoff, L., Burmeister, Y., Kraemer, K., Fuessel, S., Toma, M., Schwenzer, B., Meye, A., Grimm, M., Hakenberg, O. W., Jocham, D., Wirth, M. P."Antisense-mediated inhibition of survivin, hTERT and VEGF in bladder cancer cells in vitro and in vivo". International Journal of Oncology 32, no. 5 (2008): 1049-1056. https://doi.org/10.3892/ijo.32.5.1049