Collery Philippe, Michalke Bernhard, Lucio Marianna, Varlet Didier, Guigonis Jean-Marie, Scimeca Jean-Claude, Schmid-Antomarchi Heidy, Schmid-Alliana Annie
Société de Coordination de Recherches Thérapeutiques, Algajola, France;
Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
Anticancer Res. 2023 Mar;43(3):1017-1023. doi: 10.21873/anticanres.16246.
BACKGROUND/AIM: Rhenium(I)-diselenoether (Re-diSe) is a compound combining a rhenium tricarbonyl(I) core with a diselenide ligand. A high dose of 60 mg/kg had a pro-tumor effect in a previous study, in non-immune deficient 4T1 tumor-bearing mice, while doses of 1 and 10 mg/kg did not affect tumor growth, after repeated oral administrations. This study aimed to examine the tumor effects of a lower dose of 0.1 mg/kg with the same experimental design and to assay plasma Re and Se concentrations.
Syngenic BALB/cByJ (JAX) mice were orthotopically inoculated with 4T1 mammary breast cancer cells. Re-diSe was daily administered orally for 23 days at doses of 0.1, 1, and 10 mg/kg, whereas controls received no treatment. Tumor and mice weights were measured at the end of the experiment. Plasma Re and Se concentrations were assayed by an inductively coupled plasma sector field mass spectrometry instrument (ICP-sf-MS).
The weight of the tumors did not vary in treated versus non-treated mice. The limit of detection (LOD) of Re was 0.34 nmol/l. Plasma Re concentrations were 14±20 nmol/l at doses of 0.1 mg/kg, and increased at higher doses, up to 792±167 nmol/l at doses of 10 mg/kg. Plasma Se concentrations were significantly increased in mice treated with the dose of 0.1 mg/kg (4,262±1,511 nmol/l) versus controls (1,262±888 nmol/l), but not from 0.1 to 1 mg/kg, nor from 1 to 10 mg/kg.
The 0.1 mg/kg dose of Re-diSe resulted in detectable plasma Re concentrations and significantly increased plasma Se concentrations. In the future, doses as low as 0.1 mg/kg of Re-diSe will be tested, exploring its potential immune interest as a metronomic schedule of treatment, but in mouse models that readily develop extensive metastatic disease.
背景/目的：铼（I）-二硒醚（Re-diSe）是一种将三羰基铼（I）核心与二硒化物配体结合的化合物。在先前的一项研究中，在非免疫缺陷的4T1荷瘤小鼠中，高剂量60mg/kg具有促肿瘤作用，而在重复口服给药后，1mg/kg和10mg/kg的剂量对肿瘤生长没有影响。本研究旨在采用相同的实验设计，研究较低剂量0.1mg/kg对肿瘤的影响，并测定血浆中铼和硒的浓度。
将同基因的BALB/cByJ（JAX）小鼠原位接种4T1乳腺癌细胞。以0.1、1和10mg/kg的剂量每日口服给予Re-diSe，持续23天，而对照组不进行治疗。在实验结束时测量肿瘤和小鼠的重量。通过电感耦合等离子体质谱仪（ICP-sf-MS）测定血浆中铼和硒的浓度。
治疗组和未治疗组小鼠的肿瘤重量没有差异。铼的检测限（LOD）为0.34nmol/l。在0.1mg/kg剂量下，血浆铼浓度为14±20nmol/l，在较高剂量下升高，在10mg/kg剂量下高达792±167nmol/l。与对照组（1262±888nmol/l）相比，0.1mg/kg剂量治疗的小鼠血浆硒浓度显著升高（4262±1511nmol/l），但从0.1mg/kg到1mg/kg以及从1mg/kg到10mg/kg时没有升高。
0.1mg/kg剂量的Re-diSe导致血浆中铼浓度可检测到，且血浆硒浓度显著升高。未来，将测试低至0.
