Evaluating the anticancer properties of liposomal copper in a nude xenograft mouse model of human prostate cancer: formulation, in vitro, in vivo, histology and tissue distribution studies.
Evaluating the anticancer properties of liposomal copper in a nude xenograft mouse model of human prostate cancer: formulation, in vitro, in vivo, histology and tissue distribution studies.
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评估脂质体铜在人类前列腺癌裸异种移植小鼠模型中的抗癌特性：配方、体外、体内、组织学和组织分布研究。
DOI：
10.1007/s11095-014-1403-6
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发表时间：
2014
影响因子：
3.7
通讯作者：
Xiong,MayP
中科院分区：
文献类型：
--
作者：
Wang,Yan;Zeng,San;Lin,Tien-Min;Krugner-Higby,Lisa;Lyman,Doug;Steffen,Dana;Xiong,MayP
目的虽然铜络合物已被研究作为抗癌剂，但尚未描述铜本身作为癌症杀死剂。对隐形脂质体铜制剂 (LpCu) 进行了体外和体内研究。方法通过代谢细胞毒性测定、ROS 监测和流式细胞术对前列腺癌来源的 PC-3 细胞中的 LpCu 进行评估。通过对携带 PC-3 异种移植肿瘤的小鼠进行瘤内和静脉注射，体内评估了 LpCu 的功效。通过进行血液学和血液生化测定来评估毒理学，并通过元素分析来研究组织组织学和铜分布。结果LpCu和游离铜盐表现出相似水平的细胞代谢毒性和ROS水平。流式细胞术显示细胞死亡的机制为凋亡和坏死。动物注射了它。 3.5 mg/kg 或静脉注射3.5 和 7.0 mg/kg LpCu 表现出显着的肿瘤生长抑制作用。肾脏和眼睛是受Cu介导毒性影响的主要器官，而脾脏和肝脏是Cu沉积的主要器官。结论LpCu可有效减轻异种移植前列腺癌模型中的肿瘤负荷。对于接受最大耐受剂量 LpCu 7.0 mg/kg 治疗的动物，有组织学证据表明其肾脏和眼睛存在铜毒性。
PurposeAlthough Cu complexes have been investigated as anticancer agents, there has been no description of Cu itself as a cancer killing agent. A stealth liposomal Cu formulation (LpCu) was studiedin vitroandin vivo.MethodsLpCu was evaluated in prostate cancer origin PC-3 cells by a metabolic cytotoxicity assay, by monitoring ROS, and by flow cytometry. LpCu efficacy was evaluatedin vivousing intratumoral and intravenous injections into mice bearing PC-3 xenograft tumors. Toxicology was assessed by performing hematological and blood biochemistry assays, and tissue histology and Cu distribution was investigated by elemental analysis.ResultsLpCu and free Cu salts displayed similar levels of cell metabolic toxicity and ROS. Flow cytometry indicated that the mechanisms of cell death were both apoptosis and necrosis. Animals injected i.t. with 3.5 mg/kg or i.v. with 3.5 and 7.0 mg/kg LpCu exhibited significant tumor growth inhibition. Kidney and eye were the main organs affected by Cu-mediated toxicities, but spleen and liver were the major organs of Cu deposition.ConclusionsLpCu was effective at reducing tumor burden in the xenograft prostate cancer model. There was histological evidence of Cu toxicity in kidneys and eyes of animals treated at the maximum tolerated dose of LpCu 7.0 mg/kg.