Study On MEK Inhibitors Of Series Compounds For Anti-Tumor Effect On A549 Cells In Vitro

OBJECTIVE:To observe the anti-tumor effect of the 9 mitogen-activated protein kinase kinase(MEK) inhibitors of CQN series compounds on A549 cells, and evaluate the antitumor effect and mechanism of the high bioactive compounds in vitro.METHODS:(1) Screen the 9 CQN series of MEK inhibitors through proliferation assay of A549 cell (K-ras mutation) to choose the significant one(s).(2) The phosphorylation of ERK1/2 was detected by ELISA.(3) The activity of the compounds was measured by flow cytometry and wound-healing for the effect on the cell cycle, apoptosis and cell migration ability, respectively.RESULTS:(1) According to the proliferation assay,2 compounds (CQN-4, CQN-5) were selected, which have the equivalent anti-tumor effect to trametinib in the proliferation assay.(2) ELISA showed, with the two compounds, the phosphorylation of ERK1/2 in A549 cells was significantly inhibited, which was in a dose-dependent manner.(3) Flow cytometry showed considerable effect of CQN-4 and CQN-5 in the cell cycle and cell apoptosis assay. The two selected compounds have obvious block effect to the G1 phase (P<0.01) and lead to obvious apoptosis (P<0.01), which was in a dose-dependent manner.(4) The study of Cell wound-healing showed the compounds were demonstrated significant inhibiting activity of the cell migration ability.