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首页> 美国卫生研究院文献>Scientific Reports >A super gene expression system enhances the anti-glioma effects of adenovirus-mediated REIC/Dkk-3 gene therapy
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A super gene expression system enhances the anti-glioma effects of adenovirus-mediated REIC/Dkk-3 gene therapy

机译：超基因表达系统增强了腺病毒介导的REIC / Dkk-3基因治疗的抗神经胶质瘤作用

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Reduced expression in immortalized cells/Dickkopf-3 (REIC/Dkk-3) is a tumor suppressor and therapeutic gene in many human cancers. Recently, an adenovirus REIC vector with the super gene expression system (Ad-SGE-REIC) was developed to increase REIC/Dkk-3 expression and enhance therapeutic effects compared with the conventional adenoviral vector (Ad-CAG-REIC). In this study, we investigated the in vitro and in vivo effects of Ad-SGE-REIC on malignant glioma. In U87ΔEGFR and GL261 glioma cells, western blotting confirmed that robust upregulation of REIC/Dkk-3 expression occurred in Ad-SGE-REIC-transduced cells, most notably after transduction at a multiplicity of infection of 10. Cytotoxicity assays showed that Ad-SGE-REIC resulted in a time-dependent and significant reduction in the number of malignant glioma cells attaching to the bottom of culture wells. Xenograft and syngeneic mouse intracranial glioma models treated with Ad-SGE-REIC had significantly longer survival than those treated with the control vector Ad-LacZ or with Ad-CAG-REIC. This study demonstrated the anti-glioma effect of Ad-SGE-REIC, which may represent a promising strategy for the treatment of malignant glioma.
机译：在永生化细胞/ Dickkopf-3（REIC / Dkk-3）中减少的表达是许多人类癌症中的抑癌基因和治疗基因。近来，与常规腺病毒载体（Ad-CAG-REIC）相比，开发了具有超基因表达系统的腺病毒REIC载体（Ad-SGE-REIC）以增加REIC / Dkk-3表达并增强治疗效果。在这项研究中，我们调查了Ad-SGE-REIC对恶性神经胶质瘤的体外和体内作用。在U87ΔEGFR和GL261神经胶质瘤细胞中，蛋白质印迹证实Ad-SGE-REIC转导的细胞中REIC / Dkk-3表达强烈上调，尤其是在感染10次后转导后。细胞毒性试验表明，Ad-SGE -REIC导致附着在培养孔底部的恶性神经胶质瘤细胞数量随时间而显着减少。用Ad-SGE-REIC治疗的异种移植物和同基因小鼠颅内神经胶质瘤模型的存活时间明显长于用对照载体Ad-LacZ或Ad-CAG-REIC治疗的模型。这项研究证明了Ad-SGE-REIC的抗神经胶质瘤作用，这可能代表了治疗恶性神经胶质瘤的一种有前途的策略。

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