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铼(I)-二硒醚作为抗癌药物在多次给药后对荷耐药性乳腺肿瘤小鼠的剂量效应

Dose Effect of Rhenium (I)-diselenoether as Anticancer Drug in Resistant Breast Tumor-bearing Mice After Repeated Administrations.

作者信息

Collery Philippe, Santoni François, Ciccolini Joseph, Tran Thi Ngoc Nga, Mohsen Ahmed, Desmaele Didier

机构信息

Society for the Coordination of Research, Algajola, France

Association of Research and Development Center for the Therapeutic Use of Organo-Metallic Compounds, Polyclinic Maymard, Bastia, France.

出版信息

Anticancer Res. 2016 Nov;36(11):6051-6057. doi: 10.21873/anticanres.11194.

Abstract

Rhenium (I)-diselenoether has shown promising antiproliferative efficacy in both in vitro and in vivo models. However, the maximal tolerated dose and dose-effect relationships have not been fully addressed for this compound. Here, we evaluated the tolerance and efficacy of three dose-levels (namely 10, 40 and 100 mg/kg) intraperitoneally administered daily over 28 days in mice bearing the resistant MDA-MB231 breast cancer cell line. The upper dose was found to be toxic and was reduced to 60 mg/kg. The 10 mg/kg dose well tolerated, whereas 40 mg/kg was associated with 10% mortality (LD). Both 10 and 40 mg/kg dosing achieved a significantly similar regression of tumor growth compared with untreated animals. This study suggests that 10 mg/kg daily is the recommended dose for rhenium (I) diselenoether.

摘要

铼(I)-二硒醚在体外和体内模型中均显示出有前景的抗增殖功效。然而,该化合物的最大耐受剂量和剂量效应关系尚未得到充分研究。在此,我们评估了在携带耐药性MDA-MB231乳腺癌细胞系的小鼠中,连续28天每天腹腔注射三种剂量水平(即10、40和100mg/kg)的耐受性和疗效。发现较高剂量有毒,遂将其降至60mg/kg。10mg/kg剂量耐受性良好,而40mg/kg剂量有10%的死亡率(LD)。与未治疗的动物相比,10mg/kg和40mg/kg剂量均使肿瘤生长出现显著相似的消退。本研究表明,铼(I)二硒醚的推荐剂量为每日10mg/kg。

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