Abstract
BackgroundAstrocyte-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.MethodsIn 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.ResultsThe 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.ConclusionWe 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.
Highlights
Astrocyte-elevated gene-1 (AEG-1) is over-expressed in many cancer cells and has multiple key functions in tumor initiation and progression
We developed a novel adenovirusmediated anti-AEG-1 Single-chain antibody fragment (ScFv) expression system driven by stathmin promoter, the dual-specificity of which is respectively from anti-AEG-1 ScFv and tumor specific promoter
Recombinant AEG‐1 ScFv expressed in cervical cancer cells To confirm that the anti-AEG-1 ScFv fusion gene could express correctly within the cervical tumor cells, we constructed recombinant AEG-1 ScFv expression plasmid pcDNA3.1-SFv and the control vector, and transfected these two vectors into HeLa and SiHa cells, respectively
Summary
Astrocyte-elevated gene-1 (AEG-1) is over-expressed in many cancer cells and has multiple key functions in tumor initiation and progression. Targeted-AEG-1 siRNA is one of the most common techniques to downregulate AEG-1 expression, but the lack of tumor specificity and available delivery system make it difficult to enter clinical trials. Astrocyte-elevated gene-1 (AEG-1), called mataderin (MTDH) or LYRIC, was firstly cloned in human fetal astrocytes infected by HIV in 2002 [1]. It becomes increasingly hot in the field of tumor research, for the expression level of AEG-1 is abnormally high in various kinds of cancers [2,3,4] while extremely low in normal tissues, which suggests that AEG-1 may involve in tumorigenesis and represent a valuable biomarker. CAR-T with anti-CD19 ScFv has been translated into a clinical product to treat several kinds of leukemia [15]
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