Inhibitory effect of RNA interference on the expression of nuclear factor-κB in glioblastoma multiforme and its mechanism

Objective To investigate the inhibitory effect of RNA interference on the expression of nuclear factor-κB (NF-κB) in glioblastoma multiforme and its mechanism. Methods The specific target sequence and expression vector of lentivirus p65 were constructed and packed into 293T cells and then transfected into A172 cells. The mice were randomly divided into blank group, model group, low and high RNAi group and negative control group. After 14 days of subcutaneous model of mice, the RNAi lentivirus carrier particles were injected into the tail vein of the low and high RNAi mice, respectively, 50 and 100 μl (1×105 TU/μl), and the negative control group was injected with the blank carrier virus particles 100 μl (1×105 TU/μl). Results Lentivirus transfected A172 cells significantly inhibited the proliferation (P=0.000). Compared with the control group, the survival rate of the high dose group was 60%. The specific target sequence of NF-κB p65 interfered with A172 cells, and the expression level of p65 protein in the 3 RNAi groups decreased significantly (P=0.000). The results of animal experiments showed that the weight of all the mice in the other groups began to decline after 9 d, and the weight of the mice in the low dose lentivirus interference group increased in Eighteenth days, and the effect of high dose weight recovery was slightly better than the low dose interference group. The tumor volume of the mice in the model group was significantly higher than that of the two RNA interference group (P=0.000), and the tumor volume of the negative lentivirus control group was not significantly reduced. The detection of NF-κB p65 protein level in tumor tissue showed that p65 was high in model group and negative control group, and the level of p65 expression in RNA high and low dose interference group was significantly decreased (P=0.000). Inflammatory cytokines interleukin (IL)-1 beta and tumor necrosis factor-α (TNF-α) were highly expressed in the model group, and the expression of IL-1 beta and TNF-α could be effectively inhibited by p65 interference with RNA (P=0.000). Conclusion The specific interference of the expression of NF-κB p65 protein can effectively improve the pressure of tumor bearing and reduce the inflammatory response of mice under the subcutaneous implantation of glioma A172. Key words: RNA interference; Nuclear factor-κB; Glioblastoma multiforme; Inflammatory factor; p65 protein