中文摘要：

目的：研究新型小分子酪氨酸激酶抑制剂NXGH和NXGF对不同EGFR表达水平及突变状态肺癌细胞的敏感性,为构建EGFR分子分型成像探针提供参考依据。方法：构建基于NXG结构的新型小分子酪氨酸激酶抑制剂NXGH和NXGF,选择4种不同EGFR表达水平及突变状态肺癌细胞：PC9（EGFR 19外显子缺失突变）、H1975（EGFR L858R突变合并T790M二次突变）、H358（EGFR野生型表达）及H520（EGFR阴性表达）,应用MTT方法分析梯度浓度NXGH及NXGF 48 h时间点对4种肺癌细胞的抑制作用,分别计算IC_（50）及细胞存活率,比较NXGH及NXGF对不同肺癌细胞的敏感性。结果：NXGH作用下,PC9、H358、H520、H1975肺癌细胞IC_（50）分别是0.675μmo L·L~（-1）、12.097μmo L·L~（-1）、11.368μmo L·L~（-1）和0.981μmo L·L~（-1）,NXGH浓度为1.25、2.5和5μmo L·L~（-1）时,PC9和H1975细胞的IC_（50）低于H358和H520（P〈0.05）。NXGF作用下,PC9、H358、H520、H1975肿瘤细胞IC_（50）分别是0.685μmo L·L~（-1）、4.265μmo L·L~（-1）、3.097μmo L·L~（-1）和0.331μmo L·L~（-1）,NXGF浓度为1.25、2.5μmo L·L~（-1）时,PC9和H1975的IC_（50）低于H358和H520（P〈0.05）。结论：本实验室设计构建的新型小分子酪氨酸激酶抑制剂NXGH和NXGF对不同EGFR表达水平和突变状态的肺癌细胞均有较高亲和性,且低浓度时对EGFR突变型更敏感。

英文摘要：

Objective：To investigate the sensitivity of novel small molecule tyrosine kinase inhibitors NXGH and NXGF to 4 lung cancer cell lines with different EGFR expression and mutant status.Methods：Novel small molecule tyrosine kinase inhibitors NXGH and NXGF based on NXG structure were designed.Four lung cancer cell lines with different EGFR expression and mutation status：PC9（Exon19 deletion mutation）,H1975（L858R mutation combined T790 M mutation）,H358（wide EGFR expression） and H520（EGFR negative expression） were chosen.Inhibition ratio of NXGH and NXGF at different concentration（1.25,2.5,5.0,10,20,30,40,60,80 μmo L·L~（-1））against 4 lung cancer cell lines in 48 h were investigated by MTT method.IC_（50） and cell viability were calculated,and sensitivity between different cell lines were compared.Results：IC_（50） of PC9,H358,520 and H1975 cells incubated with NXGH were 0.675 μmo L·L~（-1）,12.097 μmo L·L~（-1）,11.368 μmo L·L~（-1）and 0.981 μmo L·L~（-1）,respectively.IC_（50） of PC9 and H1975 were less than H358 and H520 when the concentration was 1.25,2.5 and 5 μmo L·L~（-1）（P0.05）.IC_（50） of PC9,H358,H520 and H1975 cells incubated with NXGF were0.685μmo L·L~（-1）,4.265 μmo L·L~（-1）,3.097 μmo L·L~（-1）and 0.331 μmo L·L~（-1）,respectively.IC_（50） of PC9 and H1975 were less than H358 and H520 when the concentration was 1.25 and 5 μmo L·L~（-1）（P0.05）.Conclusion：The novel small molecule tyrosine kinase inhibitors NXGH and NXGF,which were designed and constructed in our laboratory successfully,had high affinity for lung cancer cells with different EGFR expression and mutation status.And they were more sensitive to EGFR mutant cell at low concentration as expected.