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首页> 外文期刊>Inorganic Chemistry Frontiers >Novel cyclometalated iridium(iii) phosphine-imine (PN) complexes: highly efficient anticancer and anti-lung metastasis agents
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Novel cyclometalated iridium(iii) phosphine-imine (PN) complexes: highly efficient anticancer and anti-lung metastasis agents

机译：新型环素丙酮化铱（III）膦 - 亚胺（PN）配合物：高效的抗癌和抗肺转移剂

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摘要

Herein, a new class of iridium(iii)-based metal complexes with phosphine-imine (P<^>N) ligands are synthesized and authenticated. These complexes show high cytotoxicities against seven cancer cells in vitro. Simultaneously, antitumor mechanism studies show that complex Ir3 induces apoptosis by depolarization of mitochondrial membrane potential, ROS overproduction and ROS-mediated DNA damage. Importantly, BIX01294, a G9a histone methyltransferase inhibitor, could markedly sensitize Ir3-induced cytotoxicity, cell cycle arrest, apoptosis and inhibition of migration in HCT116 cancer cells in vitro. Finally, we show that combined treatment with Ir3 and BIX01294 potently inhibits tumour growth and lung metastasis in vivo. Taken together, we demonstrate that BIX01294 could potently sensitize iridium(iii)-based metal complex-induced inhibition of tumour progression and provide the basis for developing new metal-based anticancer agents and therapeutic strategies in vivo for effective cancer therapy.
机译：这里，合成和认证了一种新的铱（III）基于磷酸亚胺（P <^> N）配体的铱（III）的金属配合物。这些复合物在体外展示针对七种癌细胞的高细胞毒性。同时，抗肿瘤机制研究表明，复杂的IR3通过线粒体膜电位的去极化，ROS生产率和ROS介导的DNA损伤诱导细胞凋亡。重要的是，G9A组甲基转移酶抑制剂Bix01294可以显着敏化IR3诱导的细胞毒性，细胞周期停滞，凋亡和在体外HCT116癌细胞中的迁移抑制。最后，我们表明使用IR3和BIX01294的组合治疗效果抑制了体内肿瘤生长和肺转移。我们携带在一起，我们证明Bix01294可以易于敏捷地敏化铱星（III）的金属复合诱导的肿瘤进展抑制，并为在体内开发新的金属抗癌剂和治疗策略提供有效癌症治疗的基础。

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