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An archaeal histone-like protein mediates efficient p53 gene transfer and facilitates its anti-cancer effect in vitro and in vivo

Cancer Gene Therapy volume 14, pages 968–975 (2007)Cite this article

Abstract

The improvement of the transfection efficiency of the non-viral-based gene delivery systems is a key issue for the application in gene therapy. We have previously described an archaeal histone-like protein-based (HPhA) gene delivery system and showed that HPhA formed stable non-covalent complexes with nucleic acids and improved their delivery by using β-galactosidase as a reporter gene. In this study, the wild-type p53 gene was transfected into the cancer cells using the HPhA as a vector, and the expression level and the activity of p53 gene were evaluated both in vitro and in vivo. Gene expression was determined by real-time reverse transcriptase-PCR and western blotting analysis. The cellular growth inhibition and apoptosis of HPhA-mediated p53 transfection were assessed by XTT (sodium 3′-[1-(phenylaminocarbonyl)-3,4-tetrazolium]-bis(4-methoxy-6-nitro)benzene sulfonic acid hydrate) assay and annexin V–FITC (fluorescein isothiocyanate) staining, respectively. Further more, transfection of HPhA/p53 into CNE (nasopharyngeal carcinoma cell line)-xenografted nude mice was performed and tumor growth was measured. The present study demonstrates that HPhA enhances the efficiency of p53 gene transfer and antitumor activity compared with the widely used Lipofectamine. These results demonstrate that HPhA enhances the in vitro and in vivo efficiency of p53 gene transfer and suggest that it may be served as a promising tool for gene delivery and gene therapy.

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Acknowledgements

We are grateful to Li-Xue Shi for her helpful contributions. This study was supported by grants from National Natural Science Foundation of China (30571642) and the 973 programs (2004CB719606).

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Authors and Affiliations

  1. Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, Jilin University, Changchun, China

    Y Y Li, R Wang, Z M Zhang, X X Fang & Y Feng

  2. Biotechnology Application Laboratory, Institute of Military Veterinary, Academy of Military Medical Science, Changchun, China

    G L Zhang, Y J Zheng & P Zhu

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Correspondence to X X Fang or Y Feng.

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Li, Y., Wang, R., Zhang, G. et al. An archaeal histone-like protein mediates efficient p53 gene transfer and facilitates its anti-cancer effect in vitro and in vivo. Cancer Gene Ther 14, 968–975 (2007). https://doi.org/10.1038/sj.cgt.7701086

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