摘要
Abstract
Objective To observe the effects of c-MET inhibitor SU11274 combined with the epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI)gefitinib or erlotinib on the proliferation and apoptosis of human lung cancer cell line PC9 / R (acquired gefitinib EGFR-TKI-resistance cell line PC9 cells)and to investigate the mechanism. Methods We cultured the human lung cancer cell line PC9 / R and divided them into six groups:the control group (group C), SU11274 group (group S),gefitinib group (group G),erlotinib group (group E),gefitinib combined with SU11274 group (group GS),and erlotinib combined with SU11274 group (group ES). The groups S,G,E,GS,and ES were added with 5 umol/ L SU11274,1 umol/ L gefitinib,1 umol/ L erlotinib,1 μmol/ L gefitinib + 5 μmol/ L SU11274,and 1 μmol/ L er-lotinib + 5 μmol/ L SU11274;group C was not added any drugs. At 72 h after administration,the cell proliferation was de-tected by using MTT method,and the apoptosis was detected by using flow cytometry. The protein expression of p-EGFR, p-STAT3,and p-AKT was detected by Western blotting. Results The cell survival rates were lower in the groups GS and ES than in the groups G and E,and the cell survival rates of the combination groups were lower than that of group S (all P< 0. 05). The cell survival rates of groups G,E,GS,and ES were lower than that of group C (all P < 0. 05),The early apoptosis rates of the groups GS and ES were higher than those of the groups G and E respectively,and both groups were lower than group S (all P < 0. 05). The early apoptosis rates of groups GS,ES,and S were higher than that of the group C (all P < 0. 05). The protein expression of p-EGFR,p-STAT3,and p-AKT of the groups GS and ES were lower than those of the groups G and E,respectively (all P < 0. 05). The protein expression of p-EGFR,p-STAT3,and p-AKT of the com-bination group was lower than that of the group S,and the protein expression of p-EGFR,p-STAT3,and p-AKT of the groups G,E,GS,and ES was lower than that of the group C (all P < 0. 05). Conclusions SU11274 combined with ge-fitinib or erlotinib can inhibit the proliferation and promote apoptosis of the EGFR-TKI resistance lung cancer cells by inhib-iting the function of EGFR pathway.关键词
非小细胞肺癌/肺癌细胞/耐药/表皮生长因子-酪氨酸激酶抑制剂/c-MET抑制剂/细胞增殖/细胞凋亡Key words
non-small-lung cancer/lung cancer cells/drug resistance/epidermal growth factor receptor-tyrosine ki-nase inhibitor/c-MET inhibitor/cell proliferation/apoptosis分类
医药卫生
