Adenovirus-mediated anti-AEG-1 ScFv expression driven by stathmin promoter inhibits tumor growth in cervical cancer

Abstract

Background: 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 downregulate AEG-1 expression, but the lack of tumor specificity and available delivery system make it difficult to enter clinical trials. Methods: 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. Results: 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. Conclusion: 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.

Silencing of B7-H4 induces intracellular oxidative stress and inhibits cell viability of breast cancer cells via downregulating PRDX3

“…Western blot analysis. Cell protein lysates were prepared and subjected to Western blotting as previously described [18]. Samples were obtained by cell lysis in RIPA buffer (Beyotime Biotechnology, China) and separated by SDS-PAGE before being tested by using ECL chemiluminescent (Bio-Rad Chemidoc MP, Singapore).…”