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(P<0.01),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(P<0.01),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。
AIM To observe the anti- tumor effects of the mitogenactivated protein kinase kinase （MEK） inhibitors--CQN series compounds on A549 cells in vitro. METHODS Screen nine CQN series compounds through proliferation assay of non- smallcell lung carcinoma （K- ras mutation） to choose the significant ones. The activity of the compounds was measured by flow cytometry and wound- healing assay, respectively. The phosphorylation of ERK1/2 was detected by ELISA. RESULTS According to the proliferation assay, two compounds （CQN- 4, CQN- 5） were selected, which had the equivalent anti- tumor effect to trametinib in the proliferation assay. CQN-4 and CQN-5 had obvious block effect on A549 cell to G1 phase. Compared with control, CQN- 4 and CQN- 5 lead to obvious apoptosis （P 〈 0.01 ） , which was in a dose- dependent manner. Compared with control, CQN-4 and CQN-5 showed inhibitory effects on phosphorylation of ERK1/2 in A549 cells, which was in a dose-dependent manner. CQN-4 and CQN-5 exhibited inhibitory effects on A549 cells migration, with dose-dependent manner. CONCLUSION CQN-4 and CQN-5 are effective MEK inhibitors, which have anti-tumor effects on A549 cell line in vitro.
出处
《中国新药与临床杂志》
CAS
CSCD
北大核心
2015年第4期296-301,共6页
Chinese Journal of New Drugs and Clinical Remedies
