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体内生物发光成像研究 8-羟基喹啉-2-甲酰基缩氨硫脲铜配合物的抗前列腺癌活性。

Anti-prostate cancer activity of 8-hydroxyquinoline-2-carboxaldehyde-thiosemicarbazide copper complexes in vivo by bioluminescence imaging.

机构信息

Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX, USA.

PET Center, Huashan Hospital, Fudan University, Shanghai, 200235, China.

出版信息

J Biol Inorg Chem. 2018 Aug;23(6):949-956. doi: 10.1007/s00775-018-1596-y. Epub 2018 Jul 13.

Abstract

Copper 8-hydroxyquinoline-2-carboxaldehyde-thiosemicarbazide complex (CuHQTS) is a copper complex with strong anticancer activity against cisplatin-resistant neuroblastoma and prostate cancer cells in vitro by cell proliferation assay or fluorescent microscopic imaging. This study aimed to evaluate anti-prostate cancer activity of CuHQTS in vivo by bioluminescence imaging (BLI) and tumor size measurement, using athymic nu/nu mice implanted with prostate cancer cells carrying luciferase reporter gene (Luc-PC3). Growth of Luc-PC3 cells (1 × 10 cells) implanted in athymic nu/nu mice treated with CuHQTS for 2 weeks was suppressed by measurement of luciferase signals (6.18 × 10 to 5.36 × 10 p/s/cm/sr) with BLI, compared with luciferase signals of Luc-PC3 cells (4.66 × 10 to 1.51 × 10 p/s/cm/sr, p < 0.05) in the mice treated with normal saline of placebo control. Moreover, the size of PC-3 xenograft tumor (126.5 ± 34.2 mm) in athymic nu/nu mice treated with CuHQTS was significantly smaller than the size of PC-3 xenograft tumor (218.6 ± 48.0 mm, p < 0.05) in athymic nu/nu mice treated with normal saline of placebo control, suggesting in vivo tumor growth inhibition activity of CuHQTS on prostate cancer. The findings of this study support further investigation of CuHQTS as a promising new anticancer agent for the treatment of metastatic prostate cancer refractory to anticancer drugs currently available.

摘要

铜 8-羟基喹啉-2-醛缩硫代氨基脲配合物(CuHQTS)是一种铜配合物,通过细胞增殖测定或荧光显微镜成像,对顺铂耐药神经母细胞瘤和前列腺癌细胞具有很强的体外抗癌活性。本研究旨在通过生物发光成像(BLI)和肿瘤大小测量,使用携带荧光素酶报告基因(Luc-PC3)的前列腺癌细胞植入的无胸腺 nu/nu 小鼠来评估 CuHQTS 的体内抗前列腺癌活性。与生理盐水安慰剂对照组中 Luc-PC3 细胞(4.66×10 到 1.51×10 p/s/cm/sr)的荧光素酶信号相比,2 周内用 CuHQTS 处理的 Luc-PC3 细胞(1×10 个细胞)的生长通过 BLI 测量受到抑制,荧光素酶信号(6.18×10 到 5.36×10 p/s/cm/sr,p<0.05)。此外,CuHQTS 处理的无胸腺 nu/nu 小鼠中 PC-3 异种移植瘤(126.5±34.2mm)的大小明显小于生理盐水安慰剂对照组中 PC-3 异种移植瘤(218.6±48.0mm,p<0.05),提示 CuHQTS 对前列腺癌具有体内肿瘤生长抑制活性。本研究的结果支持进一步研究 CuHQTS 作为一种有前途的新型抗癌药物,用于治疗目前可用的抗癌药物难治的转移性前列腺癌。

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