Based on our previous research, a series of targeting hepatocellular carcinoma complexes, [R-Glycyrrhetinic acid-CH₂C₂H-[Co₂(CO)₆] (R = H, 1; R = NSAIDs-COOH, 2–4; R = Aromatic acid, 5–7; R = Amino acid, 8–10), were synthesized. The test showed they are slow CO releasers. Using HeLa, A549, HT-29, SMMC7721 and HepG2 cells as models, their activities against tumor cell proliferation were firstly evaluated. The resulting data show all the complexes displayed a good anti-proliferation activity against the HepG2 and SMMC-7721 liver cancer cells, and their IC₅₀ values were in the range of 10.07–66.06 µM; compared with cis-platin (DDP), their activities were comparable or even better under the same condition. Among them, complexes 3, 4, 6 and 9 exhibited higher anti-proliferation activities against HepG2 and SMMC-7721 cell lines than the other cell lines. To confirm further these complexes have selectivity to the liver cells, the uptakes of complexes 3, 4, 6 and 9 by HepG2, HT-29, A549 and SMMC7721 cell lines were studied. The results show the cell uptake rates of the complexes by HepG2 cells and SMMC7721 cells were much greater than by other cells under the same condition. In following tests, the tested complexes displayed higher activities in inhibiting NF-kB, COX-2 and iNOS; and they induced HepG2 cells apoptosis by mitochondrial pathway, which assessed by staining with different fluorescent reagent DAPI, PI, Mito-Tracker Green and DCFH-DA. Meanwhile, the tested complexes up-regulated the expression levels of caspase-3 and Bax, down-regulated the Bcl-2 expression. In addition, they had no effect on zebrafish embryo survival, embryo hatching, embryonic movement, zebrafish malformation and zebrafish movement at below 0.5 µM. This suggests the complexes are potential candidates to be used in clinic for liver cancers.

根据我们先前的研究，一系列靶向肝细胞癌的复合物，[R-甘草次酸-CH ₂ C ₂ H- [Co ₂（CO）₆ ]（R = H，1 ; R = NSAIDs-COOH，2 – 4 ; R =芳族酸，5 - 7 ; R =氨基酸，8 - 10），合成。测试表明它们是缓慢的一氧化碳释放剂。以HeLa，A549，HT-29，SMMC7721和HepG2细胞为模型，首先评估了它们对肿瘤细胞增殖的活性。结果数据显示，所有复合物均对HepG2和SMMC-7721肝癌细胞及其IC表现出良好的抗增殖活性。_50个值在10.07-66.06 µM的范围内；与顺铂（DDP）相比，它们在相同条件下的活性相当甚至更好。其中，配合物3，4，6和9对HepG2和SMMC-7721的细胞系比其他细胞系显示出较高的抗增殖活性。为了确认这些进一步配合物具有选择性的肝细胞，复合物的喉管3，4，6和9通过HepG2，HT-29，A549和SMMC7721细胞系进行了研究。结果显示，在相同条件下，HepG2细胞和SMMC7721细胞对复合物的细胞摄取率远高于其他细胞。在随后的测试中，被测试的复合物在抑制NF-kB，COX-2和iNOS方面显示出更高的活性。并通过线粒体途径诱导HepG2细胞凋亡，并用不同的荧光试剂DAPI，PI，Mito-Tracker Green和DCFH-DA染色进行评估。同时，测试的复合物上调了caspase-3和Bax的表达水平，下调了Bcl-2的表达。此外，它们对低于0.5 µM的斑马鱼胚胎存活，胚胎孵化，胚胎运动，斑马鱼畸形和斑马鱼运动没有影响。