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Antitumor effect of sFlt-1 gene therapy system mediated by Bifidobacterium Infantis on Lewis lung cancer in mice

Cancer Gene Therapy volume 18, pages 884–896 (2011)Cite this article

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Abstract

Soluble fms-like tyrosine kinase receptor (sFlt-1) is a soluble form of extramembrane part of vascular endothelial growth factor receptor-1 (VEGFR-1) that has antitumor effects. Bifidobacterium Infantis is a kind of non-pathogenic and anaerobic bacteria that may have specific targeting property of hypoxic environment inside of solid tumors. The aim of this study was to construct Bifidobacterium Infantis-mediated sFlt-1 gene transferring system and investigate its antitumor effect on Lewis lung cancer (LLC) in mice. Our results demonstrated that the Bifidobacterium Infantis-mediated sFlt-1 gene transferring system was constructed successfully and the system could express sFlt-1 at the levels of gene and protein. This system could not only significantly inhibit growth of human umbilical vein endothelial cells induced by VEGF in vitro, but also inhibit the tumor growth and prolong survival time of LLC C57BL/6 mice safely. These data suggest that Bifidobacterium Infantis-mediated sFlt-1 gene transferring system presents a promising therapeutic approach for the treatment of cancer.

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Abbreviations

Flt:

fms-like tyrosine kinase receptor

VEGF:

vascular endothelial growth factor

MVD:

microvessel density

CDFI:

color Doppler flow imaging

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Acknowledgements

This work was supported by grants from the National Natural Scientific Foundation of China (Nos. 30570693 and 81070313).

Author contributions: HZ, ZJL, DDC, SHM, LCD, JPH, CY and YH designed and performed the experiments, and contributed to manuscript writing; SHM and TGL performed pathology experiments; BYM performed ultrasound experiments; and STZ and YQZ analyzed the data. All authors read and approved the final manuscript.

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Author notes

  1. H Zhu and Z Li: These two authors contributed equally to this work.

Authors and Affiliations

  1. Department of Abdominal Cancer, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China

    H Zhu, Z Li, T Liu, D Cui, Y Zhao, J He & C Yi

  2. Department of Pathophysiology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, Sichuan Province, China

    S Mao, L Deng & Y Huang

  3. Department of Oncology, Center Hospital, Bazhong, Sichuan Province, China

    S Mao

  4. Division of Ultrasonography, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China

    B Ma

  5. Department of Obstetrics and Gynecology, West China Second Hospital, Sichuan University, Chengdu, Sichuan Province, China

    S Zhou

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Correspondence to Y Huang.

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Zhu, H., Li, Z., Mao, S. et al. Antitumor effect of sFlt-1 gene therapy system mediated by Bifidobacterium Infantis on Lewis lung cancer in mice. Cancer Gene Ther 18, 884–896 (2011). https://doi.org/10.1038/cgt.2011.57

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