Inhibitory effect of Jab1-specific shRNA on the progression of human laryngeal carcinoma xenografts nude mice

Abstract

To evaluate the antitumour efficacy of shRNA plasmid specifically targeting Jab1 gene. The nude mouse tumor model was made by subcutaneous injection of human laryngeal carcinoma Hep-2 cells. The tumor growth was monitored after intratumoral injection of pJab1, pKB plasmids and saline. Jab1 and p27 expressions in tumour tissues were examined by immunohistochemistry staining and RT-PCR. Mean volume of the pJab1-treated tumors was (267.60 ± 88.19) mm(3), significantly less than that of tumors treated with pKB plasmids (832.20 ± 140.39) mm(3) or saline (895.40 ± 145.93) mm(3) (F = 36.73, P < 0.001). Immunohistochemistry showed that the expression of Jab1 protein was significantly reduced in the pJab1-treated group (32.40% ± 5.59%) compared to the control groups, whereas the expression rate of p27 protein in the pJab1 group (76.80% ± 6.30%) was significantly increased compared to the control groups (P < 0.001). The down regulation of Jab1 protein by pJab1 plasmid was consistent with mRNA expression confirmed by RT-PCR. The level of Jab1 mRNA level in the pJab1-treated group (0.65 ± 0.03) was significantly lower than the control groups (F = 558.00, P < 0.001), however, p27 mRNA, was 0.80 ± 0.02, had no significant alteration (F = 1.52,P > 0.05). The pJab1 plasmid results in downregulation of Jab1 in an xenograft tumour model of human laryngeal carcinoma Hep-2 cells and significantly inhibits the tumour growth in vivo. This suggests that pJab1 plasmid specifically targeting Jab1 gene expression could be an effective therapy for human laryngeal carcinoma.