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Photoinduced ROS regulation of apoptosis and mechanism studies of iridium(III) complex against SGC-7901 cells

机译:ROS对SGC-7901细胞凋亡的调控及铱(III)配合物的作用机理研究

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A new iridium(III) complex, [Ir(ppy)2(FBPIP)]PF6 (Ir-1), was synthesized and characterized. The cytotoxic activity of this complex against SGC-7901, PC-12, SiHa, HepG2, BEL-7402, A549, HeLa and normal LO2 cells was investigated using the MTT method. The complex showed no cytotoxic activity against the selected cell lines. However, upon irradiation, the complex displayed potent anti-proliferative activity toward SGC-7901 cells, with a low IC50 value of 6.1 ± 0.6 μM, and showed selectivity between cancer and normal cells. Apoptosis was assayed using the AO/EB staining method. The level of reactive oxygen species (ROS), mitochondrial membrane potential, autophagy and cell invasion were studied under a fluorescence microscope. The cell cycle distribution was studied by flow cytometry. The expression of caspase and Bcl-2 family proteins was investigated by western blot. Complex Ir-1 was shown to accumulate preferentially in the mitochondria of SGC-7901 cells and induced apoptosis via the mitochondrial pathway, which involved ROS generation, mitochondrial membrane potential depolarization, and Bcl-2 and caspase family member activation. These results demonstrate that the complex induces cancer cell apoptosis by acting on mitochondrial pathways.
机译:一种新的铱( III )络合物[Ir(ppy) 2 (FBPIP)] PF 6 (Ir-1),进行了合成和表征。使用MTT方法研究了该复合物对SGC-7901,PC-12,SiHa,HepG2,BEL-7402,A549,HeLa和正常LO2细胞的细胞毒活性。该复合物对所选细胞系没有细胞毒性活性。然而,经辐照后,该复合物显示出对SGC-7901细胞有效的抗增殖活性,IC 50 值较低,为6.1±0.6μM,并且在癌症之间具有选择性和正常细胞。使用AO / EB染色法测定细胞凋亡。在荧光显微镜下研究了活性氧(ROS),线粒体膜电位,自噬和细胞侵袭的水平。通过流式细胞术研究细胞周期分布。用western blot检测caspase和Bcl-2家族蛋白的表达。复合物Ir-1被证明优先在SGC-7901细胞的线粒体中积累,并通过线粒体途径诱导凋亡,该过程涉及ROS的产生,线粒体膜电位的去极化以及Bcl-2和caspase家族成员。激活。这些结果证明该复合物通过作用于线粒体途径诱导癌细胞凋亡。

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