Abstract：Objective To investigate the effect of ATP-binding cassette superfamily G member 2 (ABCG2)in gefitinib resistance in non-small cell lung cancer(NSCLC),and to provide a basis for gefitinib-resistance of NSCLC.Methods The human lung adenocarcinoma gefitinib-sensitive cell line A549 and gefitinib-resistant human lung adenocarcinoma cell line A549/GR were cultured.A549/GR cells were tested for drug resistance by MTT assay.Western blot was used to detect the expression of ABCG2 and p-AKT proteins in A549/GR and A549 cells.Phosphatidylinositol 3 kinase/serine-threonine kinase(PI3K/AKT)pathway activator insulin-like growth factor-1(IGF-1)and LY294002 acted as inhibitor were added,respectively.The expression of p-AKT and ABCG2 proteins on the above two kinds of cells were analyzed.The efflux of ABCG2 in A549 and A549/GR cell lines was determined by flow cytometry.The serum of nonsmall cell lung cancer(NSCLC)patients and healthy people treated in our hospital from April 2015 to April 2017 were collected,they were divided into NSCLC non-drug resistant group (20 cases),NSCLC Gefitinib resistance group(20 cases)and healthy group (20 cases).The expression of ABCG2 in the three groups were detected by ELISA method.Results With the increase of dose,the inhibitory effect of gefitinib on A549 cells and A549/GR cells were enhanced(P＜0.05).The resistance index of A549/GR was 13.4.Western Blot detected for drug-resistance proteins showed that the levels of ABCG2 and p-AKT in drug-resistant A549/GR cell were both higher than those in the parental cell A549.The expression of p-AKT and ABCG2 proteins were increased in A549 cells treated with IGF-1 (P＜0.05),while treated by LY294002,the levels of p-AKT and ABCG2 were both down-regulated in A549/GR cells(P＜0.05).After IGF-1 acting on A549 cells,the efflux was enhanced in A549 cells compared with that without activation(P＜0.05).After A549/GR cells being treated with LY294002,the efflux effect was decreased in A549/GR cells compared with that without activator(P＜0.05).The expression of ABCG2 in healthy participants was obviously lower than that in patients of NSCLC non-drug resistant group(P＜0.05).The expression of ABCG2 in patients of NSCLC Gefitinib resistance group was higher than that in NSCLC non-drug resistant group and healthy participants(P＜0.05).Conclusion ABCG2 plays a key role in gefitinib-resistant NSCLC.Reversal of ABCG2-mediated NSCLC-targeted drug resistance is mainly through regulation of the PI3K/AKT signaling pathway.
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