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研究新合成的小分子吡啶锰配合物Adpa-Mn(III)([(Adpa)Mn(μ2-O)2Mn(Adpa)]PF6.8H2O(Adpa=bis(2-pyridylmethyl)amino-2-propionic acid))的抗肿瘤作用,初步探索其抗肿瘤的机制。MTT分析Adpa-Mn(III)对细胞活性的影响;活细胞工作站观察GFP荧光标记组蛋白HeLa细胞的细胞核形态,MDC染色以及GFP-LC3质粒转染,探讨细胞死亡的方式;JC-1染色检测线粒体膜电位;Fluo-3-AM和DCFH-DA荧光探针分别检测细胞中Ca2+和ROS的含量。结果发现,Adpa-Mn(III)剂量依赖性地抑制细胞活性;给药后细胞核出现固缩、片段化;自噬小泡增多,GFP-LC3荧光强度增强;线粒体膜电位下降;细胞内Ca2+发生超载,ROS含量升高。由此,Adpa-Mn(III)可抑制肿瘤细胞活性,其机制与引起线粒体膜电位下降、增加ROS生成及诱导细胞的死亡有关,同时胞内Ca2+超载也参与了该作用。这些数据显示,Adpa-Mn(III)具有成为抗肿瘤先导金属配合物的潜在可能性。
(Adpa) Mn (μ2-O) 2Mn (Adpa)] PF6.8H2O (Adpa = bis (2-pyridylmethyl) amino-2-propionic acid )) Anti-tumor effect, to explore its anti-tumor mechanism. The effect of Adpa-Mn (III) on the cell viability was analyzed by MTT. The cell morphology of GFP fluorescently labeled histone HeLa cells, MDC staining and GFP-LC3 plasmid transfection were observed by live cell workstation. Mitochondrial membrane potential; Fluo-3-AM and DCFH-DA fluorescent probe were detected in the content of Ca2 + and ROS. The results showed that Adpa-Mn (III) inhibited cell viability in a dose-dependent manner; pyknosis and fragmentation of nuclei were observed after administration; autophagic vesicles increased, GFP-LC3 fluorescence intensity increased; mitochondrial membrane potential decreased; intracellular Ca2 + Overload, ROS content increased. Thus, Adpa-Mn (III) can inhibit the activity of tumor cells, the mechanism of which is related to the decrease of mitochondrial membrane potential, increase of ROS generation and induction of cell death. Meanwhile, intracellular Ca2 + overload is also involved. These data show that Adpa-Mn (III) has the potential to become an antitumor leader metal complex.