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首页> 外文期刊>Gene Therapy and Molecular Biology >Suppression of Primary and Disseminated MurineTumor Growth with eIF5A1 Gene Therapy
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Suppression of Primary and Disseminated MurineTumor Growth with eIF5A1 Gene Therapy

机译：eIF5A1基因治疗抑制原发性和弥漫性鼠肿瘤的生长

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Eukaryotic translation initiation factor (eIF5A) is the only known protein that is post-translationally modified to contain hypusine. The purpose of this study was to establish whether eIF5A1 gene delivery might be an effective therapy against primary and disseminated tumors. The effects of adenoviral-mediated eIF5A1 gene transfer on tumor growth and animal survival were examined using a syngeneic murine melanoma (B16-F0) model and a human lung xenograft (A549) model. Significant suppression was observed in both primary melanoma (p < 0.001; B16-F0) and lung tumor (p < 0.001; A549) growth following intra-tumoral injections of Ad-eIF5A1. Increased incidence of apoptosis was evident in melanoma tumors following Ad-eIF5A1 treatment. Gene transfer of the second member of the eIF5A family, eIF5A2, also gave rise to significant delays in growth of primary melanoma tumors. Animal survival experiments revealed prolonged survival [median survival time: 25 days (treated), 7 days (control) for B16-F0; and 54 days (treated), 24 days (control) for A549]. Systemic administration of DOTAP:pCpG- eIF5A1 complexes into C57BL/6 mice suppressed tumor growth (p < 0.05) in a B16-F10 model of experimental disseminated metastases. Our findings suggest that eIF5A1 may be an important target in the development oftreatments for primary and disseminated cancers.
机译：真核翻译起始因子（eIF5A）是唯一已知的经过翻译后修饰的含有酪氨酸的蛋白质。这项研究的目的是确定eIF5A1基因递送是否可能是针对原发性和弥漫性肿瘤的有效疗法。腺病毒介导的eIF5A1基因转移对肿瘤生长和动物存活的影响使用同系鼠黑色素瘤（B16-F0）模型和人肺异种移植（A549）模型进行了检查。肿瘤内注射Ad-eIF5A1后，原发性黑素瘤（p <0.001; B16-F0）和肺部肿瘤（p <0.001; A549）的生长均受到明显抑制。 Ad-eIF5A1治疗后，黑色素瘤肿瘤细胞凋亡的发生率增加。 eIF5A家族第二个成员eIF5A2的基因转移也导致原发性黑素瘤肿瘤生长显着延迟。动物存活实验表明，存活时间延长了[中位存活时间：B16-F0为25天（治疗），7天（对照）; A549的54天（治疗），24天（对照）]。将DOTAP：pCpG-eIF5A1复合物系统给药于C57BL / 6小鼠可抑制实验性转移的B16-F10模型中的肿瘤生长（p <0.05）。我们的发现表明，eIF5A1可能是开发原发性和弥散性癌症的重要靶标。

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