Role of JNK signaling pathway in paclitaxel-induced apoptosis in hippocampal neurons of rats: the relationship with NF-κB pathway

Abstract

Objective To evaluate the role of c-Jun N-terminal kinase(JNK)signaling pathway in paclitaxel-induced apoptosis in hippocampal neurons of rats, and the relationship with nuclear factor kappa B(NF-κB)pathway. Methods The primarily cultured hippocampal neurons were seeded in 96-well plate at a density of 1×106 cells/ml(200 μl/hole), and were randomly divided into 4 groups(n=8 each)using a random number table: control group(C group), paclitaxel group(P group), JNK inhibitor SP600125 group(S group), and SP600125 + paclitaxel group(S+ P group). Paclitaxel 2 ml(1 μmol/L)was added to group P. SP600125 2 ml(10 μmol/L)was added to group S. In group S+ P, SP600125 2 ml(10 μmol/L)was added, the cell were then incubated for 1 h, and then paclitaxel 2 ml(1 μmol/L)was added.The cells were then incubated for 24 h. At 24 h of incubation, the apoptosis in hippocampal neurons was detected by flow cytometry, and the expression of NF-κB p65 was measured by Western blot.The apoptosis rate was calculated. Results Compared with group C, the apoptosis rate was significantly increased, and the expression of NF-κB p65 was up-regulated in P and S+ P groups, and the apoptosis rate was significantly decreased, and the expression of NF-κB p65 was down-regulated in group S(P<0.05). Compared with group P, the apoptosis rate was significantly decreased, and the expression of NF-κB p65 was down-regulated in group S+ P(P<0.05). Conclusion JNK signaling pathway mediates paclitaxel-induced apoptosis in hippocampal neurons of rats, and the mechanism is likely related to inhibition of NF-κB pathway activation. Key words: Paclitaxel; Neurons; Hippocampus; Apoptosis; JNK mitogen-activated protein kinases; NF-κB