ApoG2 sensitized EGFR－TKI－resistant non－small cell lung cancer cells to gefitinib

LIAO Xue-yang; SHUAI Shuai; CHEN Dong-jie; WANG Hai-xia; WANG Sen-ming

doi:10.3969/j.issn.1001-9448.2018.12.001

Abstract：Objective To investigate the inhibitory effect of a new derivative of (－)－gossypol, ApoG2, on hu-man non－small cell lung cancer (NSCLC) gefitinib resistant cell line PC9/GR and the possible underlying mechanisms. Methods Different concentrations of gefitinib , ApoG2 or the combination of two drugs were adopted on PC 9/GR cells for 48h.The cell proliferation inhibition rate was detected by CCK 8 method.PC9/GR cells were divided into four groups :control group, gefitinib group, ApoG2 group and combination group.The effect of drugs on clone formation ability of PC 9/GR cells was determined by clone formation assay.The apoptosis rate was detected by flow cytometry assay.The expres-sion of Bcl－2, Bax and Caspase －3 protein was assessed by Western Blot.Results The results of CCK8 assay showed that PC9/GR cells were resistant to gefitinib, gefitinib or ApoG2 inhibited the proliferation of PC9/GR cells in a dose－dependent manner.ApoG2 (10 mol/L) combined with gefitinib significantly reversed the resistance of NSCLC to gefitinib (P＜0.01).The combination therapy significantly inhibited the clone formation ability (P＜0.01) of PC9/GR cells and increased the apoptosis rate (P＜0.01).Western Blot showed that in the combination group , the expression of Bcl －2 protein was significantly down －regulated (P＜0.05), the expression of Bax protein and Caspase －3 protein were signifi-cantly up－regulated (P＜0.05).Conclusion Low dose of ApoG2 can reverse the resistance of NSCLC to the treatment of gefitinib.The combination of ApoG2 and gefitinib can significantly inhibit the proliferation and clone formation ability of PC9/GR cells in vitro and increase of apoptosis rate.