新型吡啶氮唑氮芥化合物与线粒体的作用及其抗肿瘤活性

Effect of Novel Pyridine Nitrogen Mustard Compound onMitochondria and Its Anti-tumor Activity

线粒体是抗肿瘤药物的重要靶点,研究药物分子与线粒体之间的作用有助于明确药物作用机制。设计并合成了靶向线粒体类抗肿瘤药物新型吡啶氮唑氮芥化合物N,N'-(1,1'-(吡啶-2,6-二取代双(亚甲基))双(1H-1,2,3-三唑-4,1-二基))双(亚甲基)双(2-氯-N-(2-氯乙基)乙胺),探究了其抗肿瘤作用机制,用MTT法检测了该化合物的细胞毒性作用,发现其对A549细胞表现出良好的抑制作用。该化合物作用于A549细胞引起细胞凋亡,DCFH-DA及JC-1染色表明该化合物通过引发细胞内ROS水平升高,继而引发线粒体功能障碍,途径诱导A549细胞凋亡。WB结果表明细胞凋亡的线粒体途径中凋亡促进蛋白Bax表达水平升高,凋亡抑制蛋白Bcl-2表达水平降低,进一步证实了该化合物通过线粒体途径引发A549细胞凋亡。

Mitochondria are important targets of anti-tumor drugs.Studying the interaction between drug molecules and mitochondria will help clarify the mechanism of drug action.A novel pyridine nitrogen mustard compound N,N'-(1,1'-(pyridine-2,6-disubstituted bis(methylene))bis(1H-1,2,3-triazole-4,1-diyl))bis(Methylene)bis(2-chloro-N-(2-chloroethyl)ethylamine)was designed and synthesized and its antitumor mechanism was explored.The MTT kit was used to detect the cytotoxicity of this compound,and it was found that the compound showed a good inhibitory effect on A549 cell.The compound acted on A549 cell leading to cell apoptosis.DCFH-DA and JC-1 staining indicated that the compound induced A549 cell apoptosis by triggering the increase of intracellular ROS levels,which in turn triggered mitochondrial dysfunction pathway.WB results showed that the pro-apoptotic gene Bax protein expression increased in the mitochondrial pathway of apoptosis,and the apoptosis inhibitor gene Bcl-2 expression decreased at the protein level,further confirming that the compound triggered A549 cell apoptosis through the mitochondrial pathway.