缩氨基硫脲类化合物D331对人肺癌A549细胞的抑制作用及机制  

Inhibitory effect induced by the thiosemicarbazone compound D331 in A549 cells and its mechanism

作　　者：祝海川[1,2] 林坚[3] 林莉[2] 杨艳燕[1] 钟武[2] 

机构地区：[1]湖北大学生命科学学院,武汉430062 [2]军事医学科学院毒物药物研究所,北京100850 [3]北京大学合成与功能生物分子中心,北京100871

出　　处：《国际药学研究杂志》2013年第2期203-207,共5页Journal of International Pharmaceutical Research

基　　金：国家科技支撑计划项目(2011BAI18B01)

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。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（P[） 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 ASd9 cells after 24 h was detected by Western blotting. Reasults Low concentration（15 ixmol/L） of D331 inhibited the proliferation of A549 cells, while high concentration（30 ~mol/L） induced cell death. Further, 30 p^mol/L D331 increased the expression of HIF1A in A549 cells. The combination of 13331 with HIFIA inhibitor 2-methoxyestradiol （2-ME） efficiently increased D331-induced cell death. Conclusion D331 has inhibitory effect on ASd9 cells, and its mechanism may be related to the regulation of the cell cycle and apoptosis.

关 键 词：细胞凋亡 HIF1A抑制剂 缩氨基硫脲类化合物 增效作用 

分 类 号：R734.2[医药卫生—肿瘤]