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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 in Chinese | WPRIM | ID: wpr-315059
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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Full text: Available Index: WPRIM (Western Pacific) Main subject: Pharmacology / Transplantation, Heterologous / Gene Expression Regulation, Neoplastic / Laryngeal Neoplasms / Reverse Transcriptase Polymerase Chain Reaction / MicroRNAs / RNA Interference / Cell Line, Tumor / Vascular Endothelial Growth Factor A / Bcl-X Protein Limits: Animals / Humans Language: Chinese Journal: Chinese Journal of Pathology Year: 2008 Type: Article

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Full text: Available Index: WPRIM (Western Pacific) Main subject: Pharmacology / Transplantation, Heterologous / Gene Expression Regulation, Neoplastic / Laryngeal Neoplasms / Reverse Transcriptase Polymerase Chain Reaction / MicroRNAs / RNA Interference / Cell Line, Tumor / Vascular Endothelial Growth Factor A / Bcl-X Protein Limits: Animals / Humans Language: Chinese Journal: Chinese Journal of Pathology Year: 2008 Type: Article