The study was intended to determine the antineoplastic effects of two new iridium(III) complexes [Ir(ppy)₂(PTTP)](PF₆) (1) (ppy = 2-phenylpyridine) and [Ir(piq)₂(PTTP)](PF₆) (2) (piq = 1-phenylisoquinoline, PTTP = 2-phenoxy-1,4,8,9-tetraazatriphenylene). In MTT assay, the ligand PTTP displayed ineffective inhibition on cell growth in SGC-7901, BEL-7402, HepG2 as well as NIH3T3 cell lines, while complexes 1 and 2 showed high cytotoxic activity on SGC-7901 cells with an IC₅₀ value of 0.5 ± 0.1 µM and 4.4 ± 0.6 µM, respectively. Cellular uptake, cell cloning experiments, wound healing assay and cell cycle arrest indicated that the two complexes can inhibit the cell proliferation in SGC-7901 and induce cell cycle arrest at G0/G1 phase. Additionally, reactive oxygen species (ROS) and mitochondrial membrane potential suggested that the two complexes induced cell apoptosis through disrupting mitochondrial functions. Further, western blot analysis illustrated that the two complexes caused apoptosis via regulating expression levels of Bcl-2 family proteins. Moreover, complex 1 could suppress tumor growth in vivo with an inhibitory rate of 49.41%. Altogether, these results demonstrated that complexes 1 and 2 exert a potent anticancer effect against SGC-7901 cells via mitochondrial apoptotic pathway and have a potential to be developed as antineoplastic drug candidates for human gastric cancer.

该研究旨在确定两种新的铱 (III) 配合物 [Ir(ppy) ₂ (PTTP)](PF ₆ ) ( 1 ) (ppy = 2-苯基吡啶) 和 [Ir(piq) ₂ ( PTTP)的抗肿瘤作用)](PF ₆ ) ( 2 )（piq = 1-苯基异喹啉，PTTP = 2-苯氧基-1,4,8,9-四氮杂三亚苯基）。在 MTT 试验中，配体 PTTP 对 SGC-7901、BEL-7402、HepG2 和 NIH3T3 细胞系的细胞生长显示出无效抑制，而复合物1和2对 SGC-7901 细胞显示出高细胞毒活性，IC ₅₀值分别为 0.5 ± 0.1 µM 和 4.4 ± 0.6 µM。细胞摄取、细胞克隆实验、伤口愈合实验和细胞周期阻滞表明这两种复合物可以抑制 SGC-7901 中的细胞增殖并诱导细胞周期阻滞在 G0/G1 期。此外，活性氧 (ROS) 和线粒体膜电位表明这两种复合物通过破坏线粒体功能诱导细胞凋亡。此外，蛋白质印迹分析表明这两种复合物通过调节 Bcl-2 家族蛋白的表达水平引起细胞凋亡。此外，复合物1可以抑制体内肿瘤生长，抑制率为49.41%。总之，这些结果表明配合物1和2 通过线粒体凋亡途径对 SGC-7901 细胞发挥有效的抗癌作用，并有可能被开发为人类胃癌的抗肿瘤候选药物。