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Bifidobacterium longum as a delivery system of TRAIL and endostatin cooperates with chemotherapeutic drugs to inhibit hypoxic tumor growth

Cancer Gene Therapy volume 16, pages 655–663 (2009)Cite this article

Abstract

In our previous study, we have shown that vector pBV22210 containing a chloramphenicol resistance and a cryptic plasmid pMB1 from Bifidobacterium longum strain could stably replicate and did not significantly affect the biological characteristics of B. longum. In this study, B. longum was transfected by electroporation with pBV22210 encoding the extracellular domain of TRAIL (B. longum-pBV22210-TRAIL) and its carbohydrate fermentation and growth curve were determined, and its location and inhibitory effect on tumor xenografts in mice were also examined. The results further proved that gene transfection did not change the main biochemical characteristics of B. longum. The results also showed that B. longum-pBV22210-TRAIL resulted in selective location in tumors and exhibited a definite antitumor effect on S180 osteosarcoma. In addition, when a low dosage of Adriamycin (5 mg kg−1) or B. longum-pBV22210-endostatin was combined, the antitumor effect was significantly enhanced. The successful inhibition of S180 tumor growth suggested a stable vector in B. longum for transporting anticancer genes combined with low-dose chemotherapeutic drugs or other target genes is a promising approach in cancer gene therapy.

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Acknowledgements

This work was supported by Grant 2006AA02Z19E of the 863 Project from the State Ministry of Science and Technology of China, the 985-II Project from Nanjing University and Grant BK2008150 from the Natural Science Foundation of Jiangsu Province to GXX; and grant 30670671 from the National Natural Science Foundation of China, grant BK2006713 from the Natural Science Foundation of Jiangsu Province, China and RFDP grant 20050284025 from the State Educational Ministry of China to JJW.

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Authors and Affiliations

  1. Department of Biological Science and Technology and State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, China

    B Hu, L Kou, C Li, L-P Zhu & J-J Wang

  2. School of Chemical Engineering, Nanjing University of Science and Technology, Nanjing, China

    Y-R Fan

  3. Center for Public Health Research, Medical School, Nanjing University, Nanjing, China

    Z-W Wu & G-X Xu

  4. Jiangsu Provincial Research Center for Gene Pharmaceutical Engineering and Technology, Suzhou, China

    G-X Xu

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Correspondence to J-J Wang or G-X Xu.

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Hu, B., Kou, L., Li, C. et al. Bifidobacterium longum as a delivery system of TRAIL and endostatin cooperates with chemotherapeutic drugs to inhibit hypoxic tumor growth. Cancer Gene Ther 16, 655–663 (2009). https://doi.org/10.1038/cgt.2009.7

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