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目的:探讨选择性COX-2抑制剂尼美舒利联合顺铂对肺癌A549细胞毒性的影响及其机制。方法:应用MTT法观察尼美舒利与顺铂联合对A549细胞生长的影响,荧光显微镜以及流式细胞仪观察对A549细胞诱导凋亡的作用,免疫细胞化学SP法检测对A549细胞增殖细胞核抗原(PCAN)基因蛋白表达的影响。结果:(1)尼美舒利与顺铂联合对A549细胞的抑制率,均高于单独顺铂的抑制率(P<0.01),用金正均法判断结果表明,二者联合对A549细胞显示协同或相加抑制作用。(2)尼美舒利与顺铂联合能介导A549细胞凋亡,二者联合组凋亡率显著高于顺铂单独作用组(P(0.01)。(3)尼美舒利与顺铂联合组PCNA阳性细胞表达率及光密度值,显著低于单用顺铂组(P<0.01)。结论:(1)尼美舒利能协同顺铂发挥对肺癌A549的细胞毒作用;其机制可能与尼美舒利协同顺铂介导A549细胞凋亡,以及增强顺铂下调A549细胞PCNA蛋白的表达有关。(2)推测选择性COX-2抑制剂有可能成为肺癌新型的化疗辅助因子,在肺癌的综合治疗中发挥重要作用。
Objective: To investigate the effect and mechanism of selective COX-2 inhibitor nimesulide and cisplatin on cytotoxicity of lung cancer A549 cells. Methods: The effects of nimesulide and cisplatin on the growth of A549 cells were observed by MTT assay. The apoptosis induced by A549 cells was observed by fluorescence microscopy and flow cytometry. The expressions of proliferating cell nuclear antigen (PCAN) gene protein expression. Results: (1) The inhibitory rate of nimesulide combined with cisplatin on A549 cells was higher than that of cisplatin alone (P <0.01). The results of Jinzheng Jun method showed that the combination of nimesulide and cisplatin showed that Synergistic or additive inhibition. (2) The combination of nimesulide and cisplatin could induce the apoptosis of A549 cells. The apoptosis rate of the combination group was significantly higher than that of the cisplatin alone group (P <0.01). (3) The combination of nimesulide and cisplatin (P <0.01) .Conclusion: (1) Nimesulide synergized with cisplatin to exert cytotoxic effect on A549 lung cancer.The mechanism may be associated with Nimesulide and cisplatin in A549 cells apoptosis, and enhanced cisplatin down A549 cell PCNA protein expression (2) speculated that selective COX-2 inhibitors may become a new chemotherapy of lung cancer cofactor in lung cancer The comprehensive treatment plays an important role.