奈达铂体外诱导肺腺癌A549细胞凋亡及其作用机制

摘要

目的 探讨奈达铂(NDP)体外对人肺腺癌A549细胞的影响及其作用机制.方法 采用四氮甲唑蓝(MTT)比色法检测不同浓度的NDP对A549细胞的杀伤作用,计算半数抑制浓度(IC50)；流式细胞术(FCM)测定给药前后细胞凋亡率及周期分布变化；半定量PCR分析凋亡基因Bax、Caspase-3、Caspase-9的表达情况.结果 NDP能显著抑制A549细胞的生长；FCM结果显示,10 μg/mL NDP作用A549细胞48 h后,与对照组相比,细胞凋亡明显增加[(25.14±3.97)％vs.(8.01±1.46)％]；S期细胞的比例增加[(52.73±1.66)％vs.(38.38±3.91)％],差异均有统计学意义(P＜0.05).与对照组相比,Bax、Caspase-3、Caspase-9表达增加(P＜0.05).结论 NDP可抑制A549细胞增殖,其机制可能与诱导细胞凋亡、细胞S期阻滞及上调Bax、Caspase 3和Caspase 9的表达有关.%Objective To study the effect of nedaplatin (NDP) on human adenocarcinoma of lung cancer A549 cells in vitro and its mechanism. Methods MTT assay was used to evaluate the inhibition of different concentrations of NDP treatment on A549 cells, and median inhibitory concentration (IC5C) was calculated. Cell apoptosis and cycle were detected by flow cytometry (FCM). The changes of Bax, Caspase-3 and Caspase-9 expressions at the mRNA level were quantified by RT-PCR. Results NDP inhibited the growth of A549 cells significantly in a dose-dependent manner. FCM results showed that apoptosis rate and the percentage of S-phase cells tended to increase after nedaplatin treatment compared with control groups (P<0. 05). Bax, Caspase-3 and Caspase-9 expressions also increased significantly compared with those in control groups (P<0.05). Conclusion NDP can inhibit the proliferation of A549 cells, which may be ascribed to inducing cell apoptosis, the S-phase arrest, and up-regulating Bax, Caspase-3 and Caspase-9 expressions.