Study On The Mechanism Of NS398 Induced Apoptosis In The Non-small Cell Lung Cancer A549 Cells

Non-steroidal anti-inflammatory drugs (NSAIDs) can induce the apoptosis of many tumor cells to inhibit their growth. Research has shown that as a kind of NSAIDs, NS398 can also induce tumor apoptosis through other pathways in addition to inhibit the expression of COX-2. This thesis is aimed to observe the effect of NS398 and to investigate the mechanism of apoptosis on A549 cell.The research mainly experiments the growth inhibition of A549 cell by MTT assay and the apoptosis was detected by morphology, meanwhile, the expression of survivin, caspase-3 mRNA were quantified by RT-PCR and the expression of caspase-3 and p-AKT protein were detected by Western blot. The results of MTT showed that NS398 could inhibit A549 cell growth, after treated 48 hours, the inhibition rate of NS398(400μmol/L) on the A549 cells could up to 66.95%, at the same time, morphological experiment was revealed that nuclear plastids was green and the cells were characterized by apoptosis of nuclear fragmentation, The expression of survivin mRNA was significantly reduced (P<0.05, P<0.01, P<0.001)and a signficiant incresae of caspase-3 mRNA was observed (P<0.05, P<0.001) in the experiment group that NS398 had added into the cell for 48 hours when compared to the control group, these results were all shown dose-dependent. On the other hand, the protein of survivin and p-AKT was expressed at a low level(P<0.01, P<0.001)and the protein of caspase-3 was increased significantly (P<0.05, P<0.001) in the experiment group that NS398 had added into the cell for 48 hours, they were also shown dose-dependent. Our study provides that NS398 can induce the apoptosis of A549 cell to inhibit tumor growth, it may be related to inhibit the phosphorylation of AKT and reduce the expression of survivin protein. It also provides theoretical basis and experimental evidence for the clinical application of NS398 on prevention and treatment of lung cancer.