Mechanism Of BPI-15086 On EGFR-T790M In Vitro

Objective: To investigate the effect of BPI-15086 on the proliferation of human lung adenocarcinoma cell line PC9 carrying EGFR wild-type human lung adenocarcinoma cell line A549,carrying EGFR 19 exon-sensitive mutations,and human lung adenocarcinoma cell line H1975 carrying EGFR T790 M mutation Role and effect of EGFR downstream signaling pathway protein expression.Methods: ARMS real-time PCR was used to identify the EGFR gene mutation types of three cell lines;CCK8 was used to detect the inhibition rate of A549,PC9 and H1975 cell proliferation;Western-blotting was used to detect the EGFR pathway of each cell line under the effect of different concentrations of BPI-15086,and expression levels of its downstream related pathway key proteins epidermal growth factor receptor(EGFR),protein kinase B(AKT),extracellular signal-regulated kinase(ERK),p-EGFR,p AKT and p ERK.Results: 1.BPI-15086 inhibited the proliferation of A549,PC9 and H1975 cells in a concentration-dependent manner.With the increase of BPI-15086 concentration,the proliferation inhibition rates of A549,PC9 and H1975 cells also increased gradually,the difference was statistically significant(P<0.05).2.With the increase of drug concentration of BPI-15086 on A549,PC9 and H1975 cells,the downstream expression levels of p EGFR,p AKT,p ERK and other EGFR signaling proteins was significantly down-regulated(P<0.05).Conclusion: BPI-15086 may inhibit the proliferation of A549,PC9,and H1975 cells by inhibiting the expression of phosphorylated EGFR downstream signaling pathway proteins.