Synergistic Antitumor Effect Of Combination Of Gefitinib And Quercetin On Non-small Cell Lung Cancer PC9/GR Cells

Objective:To investigate the efficacy of gefitinib（Gef）combination with quercetin（Que）on non-small cell lung cancer（NSCLC）PC9/gefitinib-resistance（GR）cells,and to explore the possible mechanism.Methods:The proliferation inhibition effects of different concentrations of Gef and Que and their combination on PC9/GR cells were detected by MTT assay,then the half inhibitory concentration(IC₅₀)and combination index（CI）values of Gef combination with Que were calculated.According to IC₅₀ values of Gef and Que,the experiment was divided into the following four groups:the control group,Gef group（treated with40μmol/L Gef）,Que group（treated with 90μmol/L Que）and Gef+Que group（treated with 40μmol/L Gef+90μmol/L Que）.The morphological changes of PC9/GR cells in different treatment group were observed under a fluorescent microscope,the apoptotic rates of PC9/GR cells in different treatment group were detected by FCM,the expression levels of phosphorylated protein kinase B（p-PKB,p-Akt）and cleaved-caspase-3 protein were detected by Western blotting.Results:The different concentrations of Gef and Que could inhibit the proliferation of PC9/GR cells（P<0.01）,with an IC₅₀ value of（41.26±2.38）μmol/L and（88.82±2.06）μmol/L,respectively.When combination Gef with Que,the combination group exhibited a synergistic effect with the CI values of Gef plus Que were all less than one.Fluorescent microscopy observed that the apoptosis morphological changes were more obvious in the combination group.The apoptotic rate in Gef combination with Que group was significantly higher than that in Gef or Que alone group（P<0.01）.The expression level of p-Akt protein was lower in Gef combination with Que group than that in Gef or Que alone group（P<0.01）,whereas the expression level of cleaved-caspase-3 protein was higher in Gef combination with Que group than that in Gef or Que alone group（P<0.01）.Conclusion:Gef combination with Que can significantly inhibit the proliferation of PC9/GR cells and has a synergistic effect.The potential mechanism may be related to down-regulation the expression level of p-Akt protein and apoptosis induction.