MEK抑制剂CQN系列化合物对A549细胞体外抗肿瘤作用

发布时间：2018-11-16 14:07

【摘要】：目的观察丝裂原激活蛋白激酶的激酶(MEK)抑制剂CQN系列化合物对A549细胞体外抗肿瘤作用。方法采用非小细胞肺癌A549细胞(K-ras突变)体外抗肿瘤增殖抑制实验对9个CQN系列MEK抑制剂进行筛选,得到具有显著抗肿瘤活性的化合物。通过流式细胞术检测化合物对细胞周期和凋亡的影响;并通过ELISA法检测化合物对肿瘤发生关键蛋白ERK1/2磷酸化的抑制作用;通过细胞划痕实验检测化合物对细胞迁移能力的影响。结果细胞增殖实验筛选出高活性化合物CQN-4和CQN-5,两者的体外抗A549细胞增殖抑制活性与对照药曲美替尼(trametinib)相当。CQN-4和CQN-5可将A549细胞阻滞于G1期,与对照相比可使细胞凋亡率明显增加(P0.01),且呈浓度依赖性。与对照相比,CQN-4和CQN-5对A549细胞ERK1/2磷酸化均有抑制作用(P0.01),且具有浓度依赖性。细胞划痕愈合实验显示CQN-4和CQN-5对A549细胞迁移有显著的抑制作用,且具有浓度依赖性。结论 MEK抑制剂化合物CQN-4和CQN-5对A549细胞具有显著的体外抗肿瘤活性。
[Abstract]:Objective to observe the anti-tumor effect of mitogen-activated protein kinase (MEK) inhibitor CQN on A549 cells in vitro. Methods NSCLC A549 cells (K-ras mutation) were used to screen 9 CQN series MEK inhibitors in vitro. The effects of the compounds on cell cycle and apoptosis were detected by flow cytometry, and the inhibitory effects of the compounds on the phosphorylation of ERK1/2, a key protein in tumor, were detected by ELISA assay. The effect of compounds on cell migration was investigated by cell scratch assay. Results the inhibitory activity of high activity compound CQN-4 and CQN-5, was similar to that of trimetinib (trametinib) in vitro. CQN-4 and CQN-5 could block A549 cells in G1 phase. Compared with the control group, the apoptosis rate was significantly increased (P0.01), and in a concentration-dependent manner. Compared with the control, both CQN-4 and CQN-5 inhibited ERK1/2 phosphorylation in A549 cells (P0.01) in a concentration-dependent manner. Cell scratch healing assay showed that CQN-4 and CQN-5 inhibited the migration of A549 cells in a dose-dependent manner. Conclusion MEK inhibitors CQN-4 and CQN-5 have significant anti-tumor activity on A549 cells in vitro.
【作者单位】：重庆医科大学生物化学与分子药理学重点实验室;重庆复创医药研究有限公司药理与毒理实验室;
【分类号】：R96

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