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Antitumor activity studies of iridium (III) polypyridine complexes-loaded liposomes against gastric tumor cell in vitro
Journal of Inorganic Biochemistry ( IF 3.9 ) Pub Date : 2021-09-14 , DOI: 10.1016/j.jinorgbio.2021.111603
Fu-Li Xie 1 , Zhi-Tong Huang 1 , Lan Bai 2 , Jian-Wei Zhu 3 , Hui-Hua Xu 3 , Qing-Qin Long 4 , Qi-Feng Guo 1 , Yong Wu 4 , Si-Hong Liu 1
Affiliation  

Two iridium (III) polypyridine complexes [Ir(ppy)2(BIP)]PF6 (ppy = 2-phenylpyridine, BIP = 2-biphenyl-1H-imidazo[4,5-f][1,10]phenanthroline, Ir1), [Ir(piq)2(BIP)]PF6 (piq = 1-phenylisoquinoline, Ir2) and their liposomes Ir1lipo and Ir2lipo were synthesized and characterized. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to evaluate cytotoxic activity against several cancer cells (A549, HepG2, SGC-7901, Bel-7402, HeLa) and non-cancer cell (mouse embryonic fibroblast, NIH3T3). The results showed that Ir1lipo displays the high cytotoxicity toward SGC-7901 with IC50 value of 5.8 ± 0.2 μM, while the complexes have no cytotoxicity toward A549, HepG2, Bel-7402 and HeLa cells. The cell colony demonstrated that the iridium (III) complexes-loaded liposomes can inhibit cell proliferation, induce cell cycle arrest at G0/G1 phase. Moreover, they also cause autophagy, induce a decrease of mitochondrial membrane potential and increase intracellular reactive oxygen species (ROS) content. These results suggest that the complexes encapsulated liposomes Ir1lipo and Ir2lipo inhibit the growth of SGC-7901 cells through a ROS-mediated mitochondrial dysfunction and activating the PI3K (phosphoinositide-3 kinase)/ AKT (protein kinase B) signaling pathways.



中文翻译:

铱(III)多吡啶复合物负载脂质体对胃肿瘤细胞的体外抗肿瘤活性研究

两个铱 (III) 多吡啶配合物 [Ir(ppy) 2 (BIP)]PF 6 (ppy = 2-苯基吡啶, BIP = 2-biphenyl-1 H-咪唑并[4,5-f][1,10]菲咯啉,合成并表征了Ir1 )、[Ir(piq) 2 (BIP)]PF 6 (piq = 1-苯基异喹啉、Ir2 ) 及其脂质体Ir1lipoIr2lipo。3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) 测定用于评估对几种癌细胞(A549、HepG2、SGC-7901、Bel-7402、HeLa)和非癌细胞(小鼠胚胎成纤维细胞,NIH3T3)。结果表明,Ir1lipo显示对 SGC-7901 的高细胞毒性,IC 50值为 5.8 ± 0.2 μM,而复合物对 A549、HepG2、Bel-7402 和 HeLa 细胞没有细胞毒性。细胞集落表明,负载铱(III)复合物的脂质体可以抑制细胞增殖,诱导细胞周期停滞在G0/G1期。此外,它们还引起自噬,诱导线粒体膜电位降低并增加细胞内活性氧 (ROS) 含量。这些结果表明,包裹脂质体Ir1lipoIr2lipo的复合物通过 ROS 介导的线粒体功能障碍和激活 PI3K(磷酸肌醇 3 激酶)/AKT(蛋白激酶 B)信号通路来抑制 SGC-7901 细胞的生长。

更新日期:2021-09-24
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