Objective      To determine the role of ATP-binding cassette sub-family G member 2 (ABCG2) in erlotinib resistance in non-small-cell lung cancer.       Methods      A549 cells and acquired erlotinib-resistant A549 cells (A549/ER) were separately treated with different concentrations of erlotinib for 12

24 and 48 h respectively. Real-time PCR and Western blotting were used to observe the changes of ABCG2 expressions at mRNA and protein levels. The activator (IGF-1) and inhibitor (LY294002) of PI3K/AKT pathway were used to treat A549 cells and A549/ER cells for 24 h

respectively. The expression changes of ABCG2 mRNA and p-AKT and ABCG2 were observed by real-time PCR and Western blot analysis. The efflux effect of ABCG2 after IGF-1 and LY294002 treatment was detected by flow cytometry.       Results      Compared with the A549 and A549/ER cells without erlotinib treatment

after treated by erlotinib (1

5 and 25 μmol/L) for 12

24 and 48 h

the expression of ABCG2 and inhibition or activation of PI3K/AKT signaling pathway were positively correlated with the increase of dosage and treatment time. The expression level of ABCG2 was increased in A549 cells treated with IGF-1 for 24 h and decreased in A549/ER cells treated with LY294002. In addition

the efflux effect of ABCG2 was significantly increased after IGF-1 treatment for 24 h and significantly decreased after LY294002 treatment for 24 h.       Conclusion      ABCG2 mediates erlotinib resistance in non-small-cell lung cancer by PI3K/AKT pathway

and blocking the pathway will reverse the drug resistance.