Short hairpin RNA silencing of vascular endothelial growth factor, telomerase reverse transcriptase, and Bcl-xl expression in human laryngeal squamous carcinoma xenografted in nude mice / 中华病理学杂志
Chinese Journal of Pathology
; (12): 831-836, 2008.
Article
en Zh
| WPRIM
| ID: wpr-315059
Biblioteca responsable:
WPRO
ABSTRACT
<p><b>OBJECTIVE</b>To investigate the biological impact of pEGFP-shVEGF-shTERT-shBcl-xl expression in human laryngeal squamous carcinomas xenografted in nude mice and the related antitumor mechanism.</p><p><b>METHODS</b>A recombinant plasmid vector containing 3 different short hairpin RNA (shRNA) segments including pEGFP-shVEGF-shTERT-shBcl-xl was constructed and directly injected into the grafted tumors of human laryngeal squamous carcinoma in nude mice. The mRNA and protein expressions were determined by real-time RT-PCR and Western blot respectively. Apoptosis was determined by TUNEL assay using a commercial kit. Intratumoral microvessel density (MVD) was assessed by immunhistochemistry.</p><p><b>RESULTS</b>On the 14th days after the final treatment, mRNA and protein expression of VEGF, TERT, and Bcl-xl were markedly suppressed. The tumor sizes were significantly smaller than those in the other two group, with an overall tumor inhibition ratio of 91.2%. MVD counts in the pEGFP-shVEGF-shTERT-shBcl-xl treated group were significantly lower than those of the other two groups, along with increased apoptotic cells.</p><p><b>CONCLUSIONS</b>The data showed that inhibition of VEGF, TERT, Bcl-xl expression by RNAi technique induces cellular apoptosis and suppresses the growth of laryngeal squamous carcinoma in vivo. VEGF, TERT and Bcl-xl may be involved in the development of laryngeal cancers. The findings suggest a synergistic tumor therapeutic effect through simultaneous inhibition of the three genes. Multi-target RNA interference may provide a powerful strategy against human laryngeal cancers.</p>
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Base de datos:
WPRIM
Asunto principal:
Farmacología
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Trasplante Heterólogo
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Regulación Neoplásica de la Expresión Génica
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Neoplasias Laríngeas
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Reacción en Cadena de la Polimerasa de Transcriptasa Inversa
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MicroARNs
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Interferencia de ARN
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Línea Celular Tumoral
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Factor A de Crecimiento Endotelial Vascular
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Proteína bcl-X
Límite:
Animals
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Humans
Idioma:
Zh
Revista:
Chinese Journal of Pathology
Año:
2008
Tipo del documento:
Article