Effect of silencing VEGF, c-myc, survivin and hTERT by multiple shRNA expression vectors on the xenografted human nasopharyngeal carcinoma in nude mice / 中华耳鼻咽喉头颈外科杂志

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the effects of multiple short hairpin (shRNA) expression vectors, targeting VEGF, c-myc, survivin and hTERT, genes on the xenografted human nasopharyngeal carcinoma (CNE-2Z) in nude mice.</p><p><b>METHODS</b>The shRNA expression vectors were constructed and subsequently transfected by direct injections into the tumors formed by CNE-2Z cells implanted in nude mice. The expressions of the targeted genes in tumor tissues and the apoptosis of tumor cells were evaluated.</p><p><b>RESULTS</b>NPC CNE-2Z cells were successfully inoculated and subcutaneous tumor was formed in all nude mice. Under fluorescence microscope, tumor tissues showed the expression of each vector with green fluorescence. The expression of multiple shRNAs led to the decreases in the expressions of VEGF, c-myc, survivin, hTERT mRNA and proteins. Multi-gene silencing was better than single gene silencing in inducing the apoptosis of tumor cells. Tumor growth curves showed that the tumors treated with the shRNAs, including VEGF, c-myc, survivin, hTERT or the combination of 4 shRNAs, grower slowly obviously compared with control tumors. Inhibited rates of tumor growth by VEGF-, c-myc-, survivin- and hTERT-shRNA were 46.2%, 48.5%, 51.9% and 46.8% respectively. The combined application of 4 shRNA produced the more significant inhibitory rate (82.4%) than single shRNA application.</p><p><b>CONCLUSIONS</b>The application of vector-based RNAi targeting multiple genes is a promising therapeutic modality in the gene therapy of nasopharyngeal carcinoma and multi-gene silencing is a new strategy for tumor therapy.</p>