Abstract: Objective To explore the effect of miR-23a downregulation on the gefitinib resistance in nonsmall cell lung cancer cell with the epidermal growth factor receptor （EGFR） T790M mutation. Methods The gefitinib resistance cell H1975 at logarithmic growth phase was chosen and the miR23a inhibitor was synthesized. H1975 cells were transfected with liposome to inhibit its miR23a expression （inhibition group）， and the nontransfection group without transfection and the negative control （NC） group treated with the unrelated sequence were also prepared. The transfection effect was verified by real time fluorescence quantitative PCR （qRT-PCR）. CCK-8 method was used to detect the proliferation at 24， 48， 72 and 96 h， and the drug sensitivity for gefitinib was evaluated after exposure to different doses of gefitinib （0.03～300 μmol／L）. Flow cytometry was used to detect the apoptosis rate （FITC-Annexin V／PI staining） and cell cycle （PI staining） of each group. Western blotting was used to detect the level of multidrug resistance associated protein 1 （MRP1）， lung resistance related protein （LRP） and glutathione Stransferase-π （GST-π）.
Results The level of miR23a continued to decline in inhibition group for 2496 h， all lower than those of other two groups with significant difference （P＜0.05）. The level of miR23a was （32.06±4.68）％ of non-transfection group and （31.77±3.18）％ of NC group at 96 h， respectively. The half maximal inhibitor concentration （IC50） value of gefitinib for the inhibition group was （2.82±0.46） μmol／L， all lower than those of other two groups with significant difference （P＜0.05）. Compared with the other two groups， there were increased proliferation inhibition rate， apoptosis rate and the percentage of G0／G1 phase but decreased S-G2／M phase and level of resistance proteins in inhibition group （P0.05）.Conclusion Downregulation of miR-23a overcomes gefitinib resistance in H1975 cell， and inhibits cell proliferation， induces apoptosis and cell cycle arrest， with the possible mechanism of influencing the expressions of drug resistance proteins.