Astrocyte-elevated gene-1 (AEG-1) is over-expressed in many cancer cells and has multiple key functions in tumor initiation and progression. Currently, targeted-AEG-1 siRNA is one of the most common techniques to down-regulate AEG-1 expression, but the lack of tumor specificity and available delivery system make it difficult to enter clinical trials. In this study, we creatively developed an adenovirus-mediated anti-AEG-1 single-chain antibody fragment (ScFv) expression system driven by a tumor specific promoter, and experimented with it in human cervical carcinoma cells to investigate the effect on tumor’s proliferation and apoptosis. The results showed that of HeLa and SiHa cells treated with this recombinant anti-AEG-1 ScFv adenovirus not only inhibited cell growth, but induced apoptosis both in vitro and in vivo. Furthermore, we also observed that the expressions of several apoptosis-related genes like Akt 1 and c-Myc decreased, while NF-κB (p65) and cleaved caspase 3 increased on protein levels in vivo. We concluded that stathmin promoter-driving anti-AEG-1 ScFv adenoviral system may be a breakthrough for its dual-specificity, and serve as an adjuvant tumor specific therapy method in the treatment for human cervical cancers.

中文翻译：

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由 stathmin 启动子驱动的腺病毒介导的抗 AEG-1 ScFv 表达抑制宫颈癌中的肿瘤生长

星形胶质细胞升高基因 1 (AEG-1) 在许多癌细胞中过度表达，并在肿瘤起始和进展中具有多种关键功能。目前，靶向AEG-1 siRNA是下调AEG-1表达的最常用技术之一，但缺乏肿瘤特异性和可用的递送系统使其难以进入临床试验。在这项研究中，我们创造性地开发了一种由肿瘤特异性启动子驱动的腺病毒介导的抗AEG-1单链抗体片段（ScFv）表达系统，并在人宫颈癌细胞中进行了实验，以研究其对肿瘤增殖和增殖的影响。细胞凋亡。结果表明，用这种重组抗 AEG-1 ScFv 腺病毒处理的 HeLa 和 SiHa 细胞不仅抑制细胞生长，而且在体外和体内均诱导细胞凋亡。此外，我们还观察到几种凋亡相关基因如 Akt 1 和 c-Myc 的表达降低，而 NF-κB (p65) 和裂解的 caspase 3 在体内蛋白质水平上增加。我们得出结论，stathmin 启动子驱动的抗 AEG-1 ScFv 腺病毒系统可能是其双重特异性的突破，并作为治疗人宫颈癌的辅助肿瘤特异性治疗方法。