Combined radionuclide-chemotherapy and in vivo imaging of hepatocellular carcinoma cells after transfection of a triple-gene construct, NIS, HSV1-sr39tk, and EGFP
Combined radionuclide-chemotherapy and in vivo imaging of hepatocellular carcinoma cells after transfection of a triple-gene construct, NIS, HSV1-sr39tk, and EGFP
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DOI：
10.1016/j.canlet.2009.09.004
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发表时间：
2010-04-01
期刊：
影响因子：
9.7
通讯作者：
Lee, Jaetae
中科院分区：
文献类型：
--
作者：
La Lee, You;Lee, Yong Jin;Lee, Jaetae
钠碘同向转运体 (NIS) 或突变型单纯疱疹病毒 1 型 sr39 胸苷激酶 (HSV1-sr39tk) 基因用于体内成像和癌症治疗。将 NIS 和 HSV1-sr39tk 基因转染至肝细胞癌细胞 (Huh-7/NTG) 可以增强治疗性放射性核素和鸟苷核苷类似物前药的细胞内积累，从而产生比单基因治疗更好的结果。在转染 NIS、HSV1-sr39tk 和 GFP 的肝细胞癌细胞中进行 I-124、F-18 FHBG 的非侵入性成像以及 I-131 和 GCV 的联合治疗。我们的结果表明：（1）所有三个基因在Huh-7/NTG细胞中稳定表达，（2）体外Huh-7/NTG细胞中I-125和H3-PCV摄取显着增加，（3）Huh-7/NTG的细胞存活和肿瘤生长在体外和体内均被I-131或GCV抑制，并且在联合治疗中更为显着，（4）I-124和H3-PCV的体内成像F-18 FHBG 显示 Huh-7/NTG 肿瘤中的摄取增加。我们的结果证明了使用 NIS 和 HSV1-sr39tk 进行联合基因治疗，然后对人肝细胞癌细胞进行放射性碘治疗和化疗的潜力。 (C) 2009 Elsevier Ireland Ltd. 保留所有权利。
The sodium iodine symporter (NIS) or mutant Herpes-simplex virus type1 sr39 thymidine kinase (HSV1-sr39tk) gene is used for in vivo imaging and cancer therapy. Transfection of both NIS and HSV1-sr39tk genes to hepatocellular carcinoma cells (Huh-7/NTG) could enhance intracellular accumulation of therapeutic radionuclides and guanosine nucleoside analogue prodrugs to produce better outcomes than single gene therapy. Non-invasive imaging with I-124, F-18 FHBG and combination therapy with I-131 and GCV were performed in hepatocellular carcinoma cells transfected with NIS, HSV1-sr39tk and GFP. Our results show that: (1) all three genes are stably expressed in Huh-7/NTG cells, (2) I-125 and H3-PCV uptake were markedly increased in the Huh-7/NTG cells in vitro, (3) cellular survival and tumor growth of Huh-7/NTG was inhibited by I-131 or GCV both in vitro and in vivo, and was much prominent with combination therapy, (4) in vivo imaging with I-124 and F-18 FHBG revealed increased uptake in the Huh-7/NTG tumor. Our results demonstrated the potential of combination gene therapy using NIS and HSV1-sr39tk followed by radioiodine treatment and chemotherapy in human hepatocellular carcinoma cells. (C) 2009 Elsevier Ireland Ltd. All rights reserved.