【摘要】 目的研究缩氨基硫脲类化合物双-2-吡啶基酮缩氨基硫脲(D331)对人肺癌A549细胞的抑制作用,为该类化合物治疗肺癌提供初步依据。方法首先合成了双缩氨基硫脲类化合物D331,采用细胞锥虫蓝染色法和碘化丙啶(PI)染色法测定A549细胞生长情况,并用流式细胞仪检测了细胞周期变化,Hoechst33342染色及Annexin-Ⅴ与PI双染检测细胞凋亡,Western印迹法检测A549细胞给药处理24 h后低氧诱导因子(HIF1A)蛋白的表达情况。结果 15μmol/L D331抑制A549细胞生长,而30μmol/L D331可导致A549细胞凋亡。30μmol/L的D331处理细胞24 h会引起细胞HIF1A蛋白水平的上升,而D331与HIF1A抑制剂2-甲氧基雌二醇(2-ME)联用,可增强D331导致的细胞死亡。结论 D331对人肺癌A549细胞有良好的抑制作用,其作用机制可能与调节细胞周期变化和细胞凋亡有关。更多还原

【Abstract】 Objective To evaluate the inhibitory effect of di-2-pyridylketone thiosemicarbazone(D331) on lung cancer A549 cells.Methods The compound D331 was synthesized.The growth of A549 cells was assayed by the trypan blue staining,propidium iodide(PI) staining method,and cell cycle was analyzed by flow cytometry.Further,apoptosis was analyzed by Hoechst33342 dyeing and Annexin-V and PI double staining.Expression of HIF1A in D331-treated A549 cells after 24 h was detected by Western blotting. Reasults Low concentration(15 μmol /L) of D331 inhibited the proliferation of A549 cells,while high concentration(30 μmol /L) induced cell death.Further,30 μmol / L D331 increased the expression of HIF1A in A549 cells.The combination of D331 with HIF1A inhibitor 2-methoxyestradiol(2-ME) efficiently increased D331-induced cell death.Conclusion D331 has inhibitory effect on A549 cells,and its mechanism may be related to the regulation of the cell cycle and apoptosis.更多还原