Society for the Coordination of Therapeutic Researches, 20220, Algajola, France.
Société de Coordination de Recherches Thérapeutiques, 30, avenue du port, 20220, Algajola, France.
Invest New Drugs. 2019 Oct;37(5):973-983. doi: 10.1007/s10637-019-00727-1. Epub 2019 Jan 11.
The rhenium(I)-diselenoether complex (Re-diSe) is a rhenium tricarbonyl-based drug chelated by a diselenoether ligand. In this work, we compared its inhibitory effects on the hormone-independent MDA-MB231cancer line and other different cancer cell lines after an exposure time of 72 h by MTT assays. The sensitivity of MDA-MB231 was in the same range than the hormone-dependent MCF-7 breast cancer, the PC-3 prostate and HT-29 colon cancer cells, while the A549 lung and the HeLa uterine cancer cells were less sensitive. We compared the inhibitory effects of Re-diSe and of its diselenide ligand (di-Se) on MDA-MB231 and a normal HEK-293 human embryonic cell line, after 72 h and 120 h of exposure. The cytotoxicity was also studied by flow cytometry using ethidium bromide assays, as well as the effects on the ROS production by DFCA-test, while the levels of TGF-β1, VEGF-A, IGF-1 were addressed by ELISA tests. The dose required to inhibit 50% of the proliferation (IC) of MDA-MB231 breast cancer cells decreased with the time of exposure to 120 h, while the free ligand (di-Se) was found poorly active, demonstrating the important role of Re in this Re-diSe combination. The cytotoxic effects of Re-diSe were highly selective for cancer cells, with a significant increase of the number of dead cancer cells at 5 μM for an exposure time of 120 h, while normal cells were not affected. A remarkable and significant decrease of the production of ROS together with a decrease of VEGF-A, TGF-β1, and IGF-1 by the cancer cells were also observed when cancer cells were exposed to Re-diSe.
铼（I）-二硒醚配合物（Re-diSe）是一种由二硒醚配体螯合的三羰基铼基药物。在这项工作中，我们通过 MTT 分析比较了其在 72 h 暴露时间后对激素非依赖性 MDA-MB231 癌细胞系和其他不同癌细胞系的抑制作用。MDA-MB231 的敏感性与激素依赖性 MCF-7 乳腺癌、PC-3 前列腺癌和 HT-29 结肠癌细胞相当，而 A549 肺癌和 HeLa 子宫颈癌细胞则不那么敏感。我们比较了 Re-diSe 及其二硒化物配体（di-Se）对 MDA-MB231 和正常 HEK-293 人胚胎细胞系的抑制作用，暴露时间分别为 72 h 和 120 h。还通过溴化乙锭测定法的流式细胞术研究了细胞毒性，通过 DFCA 试验研究了对 ROS 产生的影响，同时通过 ELISA 试验研究了 TGF-β1、VEGF-A 和 IGF-1 的水平。抑制 MDA-MB231 乳腺癌细胞增殖（IC）50 的所需剂量随暴露时间延长至 120 h 而降低，而游离配体（di-Se）的活性较差，表明 Re 在这种 Re-diSe 组合中起重要作用。Re-diSe 的细胞毒性作用对癌细胞具有高度选择性，在 120 h 的暴露时间下，5 μM 时癌细胞死亡数显著增加，而正常细胞不受影响。当癌细胞暴露于 Re-diSe 时，还观察到 ROS 产生显著减少，以及 VEGF-A、TGF-β1 和 IGF-1 减少。
