新型双芳基脲类化合物对非小细胞肺癌A549细胞的影响

Effects of a new bis-aryl urea compound on proliferation,cell cycle and apoptosis of lung cancer A549 cells

目的:探讨一种新型双芳基脲类化合物(代号N69B)对非小细胞肺癌A549细胞增殖、周期和凋亡的影响。方法:选择A549非小细胞肺癌细胞系,在不同浓度的N69B作用下,采用CCK-8法测定细胞增殖率、流式细胞仪测定细胞周期变化、Annexin V/PI双染法测定细胞凋亡率、Western blot法测定天冬氨酸特异性半胱氨酸蛋白酶3,8,9活性产物(Cleaved caspase-3,8,9)的相对表达量。结果:与对照组比较,N69B可抑制A549细胞的增殖,且存在明显剂量-效应和时间-效应关系(P <0.05或P <0.01);分别采用0.5、1.0和1.5μmol/L的N69B作用A549细胞24 h后,各药物组G2期细胞比例均显著性升高(P <0.01);Annexin V/PI双染结果显示,各药物组细胞凋亡率均有不同程度的升高(P <0.05或P <0.01);Western blot结果显示,随药物浓度的升高,A549细胞内Cleaved caspase-3、8、9表达量均逐渐升高。结论:N69B对A549细胞的增殖具有抑制作用,其机制可能与诱导细胞周期G2-M期阻滞及caspase介导的细胞凋亡有关。

Objective:To explore anti-cancer activities of a novel bis-aryl urea compound(code name:N69 B)using non-small cell lung cancer A549 cells. Methods:The non-small cell lung cancer A549 cells were choosed and treated by N69 B at different concentrations. The cell proliferation was quantified by CCK-8 method;the cell cycle was determined by flow cytometry;the apoptosis rate were detected by Annexin V/PI double staining;and the relative expression of Cleaved caspase-3,8,9 was measured by the Western blot. Results:Compared with the DMSO control group,N69 B inhibited the proliferation of A549 cells in manners that are time-and dose-dependent(P < 0.05 or P < 0.01). Twenty-four hours after the treatment with N69 B at 0.5,1.0 and 1.5 μM,respectively,the number of cells in G2 phase significantly increased(P < 0.01);the apoptosis rate increased in different degrees;Cleaved caspase-3,8,9 expression showed a dose-dependent elevation. Conclusion:N69 B inhibits the proliferation of A549 cells,possibly through cell cycle arrest in G2-M phase and apoptosis induced by caspase activation.