Antisense-mediated inhibition of survivin, hTERT and VEGF in bladder cancer cells in vitro and in vivo.
Int J Oncol
; 32(5): 1049-56, 2008 May.
Article
en En
| MEDLINE
| ID: mdl-18425331
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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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Neoplasias de la Vejiga Urinaria
/
Regulación Neoplásica de la Expresión Génica
/
Oligonucleótidos Antisentido
/
Telomerasa
/
ARN Interferente Pequeño
/
Interferencia de ARN
/
Factor A de Crecimiento Endotelial Vascular
/
Proteínas Asociadas a Microtúbulos
/
Proteínas de Neoplasias
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Int J Oncol
Asunto de la revista:
NEOPLASIAS
Año:
2008
Tipo del documento:
Article
País de afiliación:
Alemania