Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Bifidobacterium adolescentis as a delivery system of endostatin for cancer gene therapy: Selective inhibitor of angiogenesis and hypoxic tumor growth

Abstract

In order to overcome difficulties that hampered widespread application of antiangiogenesis in cancer therapy, a highly specific delivery system may be engaged in vivo to deliver and express antiangiogenic genes. We selected a strain of Bifidobacterium adolescentis (B. adolescentis) as the delivery system to transport endostatin gene to solid tumors. B. adolescentis with endostatin gene were injected into tumor-bearing mice through the tail vein. After the mice were sacrificed, the tumor and some normal tissues of the mice were examined. B. adolescentis were only found in the tumors and no bacilli were found in other normal tissues. Also, a strong inhibition of angiogenesis had been shown to inhibit local tumor growth in the administrated group. These results suggested that B. adolescentis only germinated and proliferated in solid tumors and might be a highly specific and efficient vector for transporting anticancer genes into target tumor in cancer gene therapy.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8

Similar content being viewed by others

References

  1. Kandel J, Bossy-Wetzel E, Radvany F, et al. Neovascularization is associated with a switch to the export of bFGF in the multistep development of fibrosarcoma. Cell. 1991;66:1095–1104.

    Article  CAS  Google Scholar 

  2. O'Reilly MS, Holmgren L, Shing Y, et al. Angiostatin: a novel angiogenesis inhibitor that mediates the suppression of metastases by a Lewis lung carcinoma. Cell. 1994;79:315–328.

    Article  CAS  Google Scholar 

  3. O'Reilly MS, Boehm T, Shing Y, et al. Endostatin: an endogenous inhibitor of angiogenesis and tumor growth. Cell. 1997;88:277–285.

    Article  CAS  Google Scholar 

  4. O'Reilly MS, Holmgren L, Chen C, et al. Angiostatin induces and sustains dormancy of human primary tumors in mice. Nat Med. 1996;2:689–692.

    Article  CAS  Google Scholar 

  5. Fan YR, Xu GX, Liu XJ, et al. Construction of a recombinant human endostatin/MBP fusion protein and study on its antitumor effects in vitro and in vivo. Chin Cancer Biother. 2000;7:150–151.

    Google Scholar 

  6. Li X, Xu GX, Wang JJ . Construction of recombinant human endostatin/MBP fusion protein and its segments and their inhibition on endothelia proliferation in vitro. Chin J Cell Biol. 2001;23:91–95.

    Google Scholar 

  7. Dachs GU, Patterson AV, Firth JD, et al. Targeting gene expression to hypoxic tumor cells. Nat Med. 1997;3:515–520.

    Article  CAS  Google Scholar 

  8. Kimura NT, Taniguchi S, Aoki K . Selective localization and growth of Bifidobacterium bifidum in mouse tumors following intravenous administration. Cancer Res. 1980;40:2061–2068.

    CAS  PubMed  Google Scholar 

  9. Yazawa K, Fujimori M, Amano J, et al. Bifidobacterium longum as a delivery system for cancer gene therapy: selective localization and growth in hypoxic tumors. Cancer Gene Ther. 2000;7:269–274.

    Article  CAS  Google Scholar 

  10. Lin PF . Antitumor effect of Actinidia chinensis polysaccharide on murine tumor. Chin J Oncol. 1988;10:441–444.

    CAS  Google Scholar 

  11. Scharek L, Hartmann L, Heinevetter L, et al. Bifidobacterium adolescentis modulates the specific immune response to another human gut bacterium, Bacteroides thetaiotaomicron, in gnotobiotic rats. Immunobiology. 2000;202:429–441.

    Article  CAS  Google Scholar 

  12. Argnani A, Leer RJ, van Luijk N, et al. A convenient and reproducible method to genetically transform bacteria of the genus Bifidobacterium. Microbiology. 1996;42:109–114.

    Article  Google Scholar 

  13. Zhang ZQ, Yao LH, Hou YD . Construction and application of a high level expression vector containing PRPL promotor. Chin J Virol. 1990;6:111–116.

    Google Scholar 

  14. Park MS, Lee KH, Ji GE . Isolation and characterization of two plasmids from Bifidobacterium longum. Lett Appl Microbiol. 1997;25:5–7.

    Article  CAS  Google Scholar 

  15. Chen J, Jin K, Chen M, et al. Early detection of DNA strand breaks in the brain after transient focal ischemia: implication for the role of DNA damage in apoptosis and neuronal cell death. Neurochemistry. 1997;69:232–245.

    Article  CAS  Google Scholar 

  16. Yasui H, Ohwaki M . Enhancement of immune response in Peyer's patch cells cultured with Bifidobacterium breve. J Dairy Sci. 1991;74:1187–1195.

    Article  CAS  Google Scholar 

  17. Reddy BS, Rivenson A . Inhibitory effect of Bifidobacterium longum on colon, mammary and liver carcinogenesis induced by 2-amino-3-methylimidazo[4,5-f] quinoline, a food mutagen. Cancer Res. 1993;53:3914–3918.

    CAS  PubMed  Google Scholar 

  18. Chen QR, Dhruv K, Sanford AS, et al. Liposomes complexed to plasmids encoding angiostatin and endostatin inhibit breast cancer in nude mice. Cancer Res. 1999;59:3308–3312.

    CAS  PubMed  Google Scholar 

  19. Sauter BV, Martinet O, Zhang WJ, et al. Adenovirus-mediated gene transfer of endostatin in vivo results in high level of transgene expression and inhibition of tumor growth and metastases. Proc Natl Acad Sci USA. 2000;97:4802–4807.

    Article  CAS  Google Scholar 

  20. Nguyen JT, Wu P, Clouse ME, et al. Adeno-associated virus–mediated delivery of antiangiogenic factors as an antitumor strategy. Cancer Res. 1998;58:5673–5677.

    CAS  PubMed  Google Scholar 

  21. Harsharnjit SG, Kay JR, Martin LC, et al. Enhancement of immunity in the elderly by dietary supplementation with the probiotic Bifidobacterium lactis HN019. Am J Clin Nutr. 2001;74:833–839.

    Article  Google Scholar 

  22. Saavedra JM, Bauman NA, Oung I, et al. Feeding of Bifidobacterium bifidum and Streptococcus thermophilus to infants in hospital for prevention of diarrhoea and shedding of rotavirus. Lancet. 1994;344:1046–1049.

    Article  CAS  Google Scholar 

  23. Walter P . Effects of vegetarian diets on aging and longevity. Nat Rev. 1997;55:S61–S65.

    CAS  Google Scholar 

  24. Kikuchi-Hayakawa H, Onodera N, Matsubara S, et al. Effects of soy milk and Bifidobacterium fermented soy milk on lipid metabolism in aged ovariectomized rats. Biosci Biotechnol Biochem. 1998;62:688–1692.

    Article  Google Scholar 

  25. Singh J, Rivenson A, Tomita M, et al. Bifidobacterium longum, a lactic acid-producing intestinal bacterium inhibits colon cancer and modulates the intermediate biomarkers of colon carcinogenesis. Carcinogenesis. 1997;18:833–841.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by Grant BK20000001 from the Natural Science Foundation of Jiangsu Province, China, to GXX; Grant 30070250 from the National Natural Science Foundation of China; and a Grant-in-aid of “985 Project” from the Nanjing University to JJW. We thank Yan Chen (New York University School of Medicine) for reading this manuscript.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Gen-Xing Xu.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Li, X., Fu, GF., Fan, YR. et al. Bifidobacterium adolescentis as a delivery system of endostatin for cancer gene therapy: Selective inhibitor of angiogenesis and hypoxic tumor growth. Cancer Gene Ther 10, 105–111 (2003). https://doi.org/10.1038/sj.cgt.7700530

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.cgt.7700530

Keywords

This article is cited by

Search

Quick links