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Journal of Experimental & Clinical Cancer Research

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Open Access 01-12-2016 | Research

Synthetic Bax-Anti Bcl₂ combination module actuated by super artificial hTERT promoter selectively inhibits malignant phenotypes of bladder cancer

Authors: Li Liu, Yuchen Liu, Tianbiao Zhang, Hanwei Wu, Muqi Lin, Chaoliang Wang, Yonghao Zhan, Qing Zhou, Baoping Qiao, Xiaojuan Sun, Qiaoxia Zhang, Xiaoqiang Guo, Guoping Zhao, Weixing Zhang, Weiren Huang

Published in: Journal of Experimental & Clinical Cancer Research | Issue 1/2016

Abstract

Background

The synthetic biology technology which enhances the specificity and efficacy of treatment is a novel try in biomedical therapy during recent years. A high frequency of somatic mutations was shown in the human telomerase reverse transcriptase (hTERT) promoter in bladder cancer, indicating that a mutational hTERT promoter might be a tumor-specific element for bladder cancer therapy. In our study, we aimed to construct a synthetic combination module driven by a super artificial hTERT promoter and to investigate its influence on the malignant phenotypes of bladder cancer.

Methods

The dual luciferase assay system was used to verify the driven efficiency and tumor-specificity of the artificial hTERT promoter and to confirm the relationship between ETS-1 and the driven efficiency of the artificial hTERT promoter. CCK-8 assay and MTT assay were used to test the effects of the Bax-Anti Bcl₂ combination module driven by the artificial hTERT promoter on cell proliferation. Simultaneously, the cell apoptosis was detected by the caspase 3ELISA assay and the flow cytometry analysis after transfection. The results of CCK-8 assay and MTT assay were analyzed by ANOVA. The independent samples t-test was used to analyze other data.

Results

We demonstrated that the artificial hTERT promoter had a higher driven efficiency which might be regulated by transcription factor ETS-1 in bladder cancer cells, compared with wild-type hTERT promoter. Meanwhile, the artificial hTERT promoter showed a strong tumor-specific effect. The cell proliferation inhibition and apoptosis induction were observed in artificial hTERT promoter- Bax-Anti Bcl₂ combination module -transfected bladder cancer 5637 and T24 cells, but not in the module -transfected normal human fibroblasts.

Conclusion

This module offers us a useful synthetic biology platform to inhibit the malignant phenotypes of bladder cancer in a more specific and effective way.

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Title: Synthetic Bax-Anti Bcl2 combination module actuated by super artificial hTERT promoter selectively inhibits malignant phenotypes of bladder cancer
Authors: Li Liu
Yuchen Liu
Tianbiao Zhang
Hanwei Wu
Muqi Lin
Chaoliang Wang
Yonghao Zhan
Qing Zhou
Baoping Qiao
Xiaojuan Sun
Qiaoxia Zhang
Xiaoqiang Guo
Guoping Zhao
Weixing Zhang
Weiren Huang
Publication date: 01-12-2016
Publisher: BioMed Central
Published in: Journal of Experimental & Clinical Cancer Research / Issue 1/2016
Electronic ISSN: 1756-9966
DOI: https://doi.org/10.1186/s13046-015-0279-6

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Abstract

Background

Methods

Results

Conclusion

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