FoxM1 Regulates Proliferation,Apoptosis And Sensitivity To Paclitaxel Of Human Nasopharyngeal Carcinoma Cells Via JNK/Mitochondrial Pathway

Objective:To investigate the effects of silencing the expression of Forkhead box M1(FoxM1 by the specific small interfering RNA(siRNA)on proliferation,apoptosis and sensitivity to paclitaxel of human nasopharyngeal carcinoma 5-8F cells,and its possible molecular mechanisms.Methods:The specific siRNA fragments targeting FoxM1 gene(FoxM1-siRNA)were transfected into nasopharyngeal carcinoma 5-8F cells,then the down-regulation effect was detected by RT-PCR,real-time fluorescent quantitative PCR and Western blotting,respectively.After transfection,the changes of proliferation and sensitivity to paclitaxel of 5-8F cells were detected by MTT assay,while cell cycle distribution and apoptosis rate were evaluated by FCM and Annexin V-FITC/PI staining assay.The protein expressions of Ki67,cyclin D1,cyclin E1,multidrug resistance 1(MDR1),multidrug resistance-associated protein 1(MRP1),c-Jun N-terminal kinase(JNK),p-JNK,c-Jun,p-c-Jun,apoptosis-related protein Bax and Bcl-2 were detected by Western blot.Result:The expressions of FoxM1 mRNA and protein in 5-8F cells after FoxMl-siRNA transfection were decreased(P<0.01).The proliferation rate of 5-8F cells transfected with FoxMl-siRNA was decreased(P<0.05),and Ki67 protein was obviously down-regulated(P<0.01).The proportion of cells in G1 phase after FoxM1 gene silencing was increased(P<0.01),while the proportion of cells in S phase was decreased(P<0.05),and the expression of Cyclin D1 and Cyclin E1 were down-regulated(P<0.01).Compared with two control groups,both MDR1(P<0.05)and MRP1(P<0.01)were down-regulated and the sensitivity of 5-8F cells to paclitaxel was significantly enhanced(P<0.01)after FoxM1-siRNA transfection.Meanwhile the apoptosis rate in siRNA/paclitaxel group was significantly higher than the negative control/paclitaxel group(P<0.01).In siRNA/paclitaxel group,the expression of p-JNK1,p-c-Jun and Bax were much higher than the negative control/paclitaxel group(P<0.01),whereas the level of Bcl-2 was down-regulated(P<0.01)Conclusion:The siRNA interfering of FoxM1 in 5-8F cells could effectively inhibit the proliferation,promote the apoptosis and enhance the sensitivity to paclitaxel ultimately by regulating the activity of JNK/mitochondrial pathway.