Antisense-mediated inhibition of survivin, hTERT and VEGF in bladder cancer cells in vitro and in vivo
| Autor: | Dieter Jocham, Oliver W. Hakenberg, Bernd Schwenzer, Marieta Toma, Ingo Kausch, Axel Meye, D. Kunze, Lena Blumhoff, Caroline E. Blietz, Manfred P. Wirth, Marc-Oliver Grimm, Yvonne Burmeister, Kai Kraemer, Susanne Fuessel, Daniela Wuttig |
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| Rok vydání: | 2008 |
| Předmět: |
Vascular Endothelial Growth Factor A
Cancer Research Small interfering RNA Telomerase Time Factors Cell Survival Survivin Transplantation Heterologous Down-Regulation Mice Nude Mice SCID Biology Transfection Inhibitor of Apoptosis Proteins Mice In vivo Cell Line Tumor Gene silencing Animals Humans Telomerase reverse transcriptase RNA Messenger RNA Small Interfering Cell Proliferation Oncogene Oligonucleotides Antisense Neoplasm Proteins Gene Expression Regulation Neoplastic Oncology Urinary Bladder Neoplasms Cancer cell Immunology Cancer research RNA Interference Microtubule-Associated Proteins |
| Zdroj: | Scopus-Elsevier |
| ISSN: | 1019-6439 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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