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Antitumor potential of SLPI promoter controlled recombinant caspase-3 expression in laryngeal carcinoma

Cancer Gene Therapy volume 19, pages 328–335 (2012)Cite this article

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Abstract

The purpose of this study is to develop a specific and efficient targeted gene therapy candidate approach for laryngeal carcinomas. Several promoters of human squamous cell carcinoma antigen 2(SCCA2), secretory leukocyte protease inhibitor (SLPI) and Survivin genes were cloned from human genomic DNA and evaluated for tumor-specific transcription potential in human laryngeal carcinoma Hep-2 cells by dual luciferase assays. One SLPI promoter fragment (677 bp) showed the highest efficiency and specificity, and was used to control the expression of a recombinant active caspases-3 (revCasp3), which could trigger apoptosis without activation of its upstream cascade elements once expressed in a cell, in an adenoviral vector (Ad-SLPI-revCasp3), and its antitumor efficacy was assessed. In vitro infection with Ad-SLPI-revCasp3 showed revCasp3 could be specifically expressed in Hep-2 cells, resulting in efficient activation of endogenous Caspase-3 and subsequent apoptosis of Hep-2 cells. In Hep-2 nude mice xenograft model, intratumoral administration of Ad-SLPI-revCasp3 significantly inhibited tumor growth without obvious loss of body weight and obvious hepatic toxicity. In summary, our study showed the specific and efficient apoptosis-inducing potential of Ad-SLPI-revCasp3, and this makes it a new candidate approach of targeted gene therapy for laryngeal squamous cell carcinoma, which needs further systematic investigation.

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Acknowledgements

The work was supported by grants from the Department of Public Health of Zhejiang Province of China (No. 2008A089, No. 2009A102 and No. 2007A086), Department of Science and Technology of Zhejiang Province (No. 2008F1029) and Department of Education of Zhejiang Province (Y200804137). We thank Ms Yuelan Chen for her technical assistance in the work.

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Author notes

  1. J Chen and B Yang: These authors contributed equally to this work and should be considered as co-first author.

Authors and Affiliations

  1. Department of Otorhinolaryngology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China

    J Chen, B Yang, S Zhang & Y Ling

  2. Clinical Research Center, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China

    J Ye & J Cao

  3. Institute of Hygiene, Zhejiang Academy of Medical Sciences, Hangzhou, China

    Z Jia

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  1. J Chen
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Correspondence to Z Jia or J Cao.

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Chen, J., Yang, B., Zhang, S. et al. Antitumor potential of SLPI promoter controlled recombinant caspase-3 expression in laryngeal carcinoma. Cancer Gene Ther 19, 328–335 (2012). https://doi.org/10.1038/cgt.2012.5

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