| 孙莹莹,孙夕林,王 凯,方 芳,申宝忠.新型小分子酪氨酸激酶抑制剂NXGH/NXGF对不同肺癌细胞的敏感性研究[J].,2017,17(27):5201-5205 |
| 新型小分子酪氨酸激酶抑制剂NXGH/NXGF对不同肺癌细胞的敏感性研究 |
| Susceptibility Evaluation of EGFR Targeted Small Molecule NXGH/NXGF for Lung Cancer Cell |
| 投稿时间：2017-03-29 修订日期：2017-04-24 |
| DOI：10.13241/j.cnki.pmb.2017.27.001 |
| 中文关键词: 小分子酪氨酸激酶抑制剂 NXGH NXGF 肺癌 表皮生长因子受体 |
| 英文关键词: Small molecule tyrosine kinase inhibitors NXGH NXGF Lung cancer Epidermal growth factor receptor |
| 基金项目:国家重点基础研究发展计划(2015CB931800)；国家自然科学基金项目(31210103913; 81471724)；黑龙江省高校分子影像重点实验室基金项目 |
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| 中文摘要: |
| 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IC50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IC50分别是0.675 μmoL?L-1、12. 097 μmoL?L-1、11.368 μmoL?L-1和0.981 μmoL?L-1，NXGH浓度为1.25、2.5和5 μmoL?L-1时，PC9和H1975细胞的IC50低于H358和H520 (P<0.05)。NXGF作用下，PC9、H358、H520、H1975肿瘤细胞IC50分别是0.685 μmoL?L-1、4.265 μmoL?L-1、3.097 μmoL?L-1和0.331 μmoL?L-1，NXGF浓度为1.25、2.5 μmoL?L-1时，PC9和H1975的IC50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: |
| ABSTRACT 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(Exon 19 deletion mutation), H1975(L858R mutation combined T790M mutation), H358(wide EGFR expression) and H520(EGFR negative ex- pression) were chosen. Inhibition ratio of NXGH and NXGF at different concentration (1.25, 2.5, 5.0, 10, 20, 30, 40, 60, 80 μmoL?L-1) against 4 lung cancer cell lines in 48 h were investigated by MTT method. IC50 and cell viability were calculated, and sensitivity be- tween different cell lines were compared. Results: IC50 of PC9, H358, 520 and H1975 cells incubated with NXGH were 0.675 μmoL?L-1, 12. 097 μmoL?L-1, 11.368 μmoL?L-1 and 0.981 μmoL?L-1，respectively. IC50 of PC9 and H1975 were less than H358 and H520 when the concentration was 1.25, 2.5 and 5 μmoL?L-1 (P<0.05). IC50 of PC9, H358, H520 and H1975 cells incubated with NXGF were0.685 μmoL?L-1, 4.265 μmoL?L-1, 3.097 μmoL?L-1 and 0.331 μmoL?L-1, respectively. IC50 of PC9 and H1975 were less than H358 and H520 when the concentration was 1.25 and 5 μmoL?L-1 (P<0.05). 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. |
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