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Open Access Research article

Inhibitory effect of Bifidobacterium infantis-mediated sKDR prokaryotic expression system on angiogenesis and growth of Lewis lung cancer in mice

Zhao-Jun Li1, Hong Zhu1, Bu-Yun Ma2, Fen Zhao3, Shu-Hua Mao34, Tai-Guo Liu1, Jian-Ping He1, Li-Cong Deng3, Cheng Yi1* and Ying Huang3*

Author Affiliations

1 Department of Abdominal Cancer, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan Province, China

2 Division of Ultrasonography, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan Province, China

3 Department of Pathophysiology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, 610041, Sichuan Province, China

4 Department of Oncology, Center Hospital, Bazhong, 636000, Sichuan Province, China

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BMC Cancer 2012, 12:155  doi:10.1186/1471-2407-12-155

Published: 26 April 2012

Abstract

Background

To construct the Bifidobacterium infantis-mediated soluble kinase insert domain receptor (sKDR) prokaryotic expression system and to observe its inhibitory effect on growth of human umbilicus vessel endothelial cells (HUVECs) in vitro and Lewis lung cancer (LLC) on mice in vivo.

Methods

The Bifidobacterium infantis-mediated sKDR prokaryotic expression system was constructed through electroporation and subsequently identified through PCR and Western blot analysis. HUVECs were added to the products of this system to evaluate the anti-angiogenesis effect through MTT assay in vitro. The LLC mice models were divided into three groups: one group treated with saline (group a); one group treated with recombinant Bifidobacterium infantis containing pTRKH2-PsT plasmid group (group b); and one group treated with recombinant Bifidobacterium infantis containing pTRKH2-PsT/sKDR plasmid group (group c). The quality of life and survival of mice were recorded. Tumor volume, tumor weight, inhibitive rate, and necrosis rate of tumor were also evaluated. Necrosis of tumor and signals of blood flow in tumors were detected through color Doppler ultrasound. In addition, microvessel density (MVD) of the tumor tissues was assessed through CD31 immunohistochemical analysis.

Results

The positively transformed Bifidobacterium infantis with recombinant pTRKH2-PsT/sKDR plasmid was established, and was able to express sKDR at gene and protein levels. The proliferation of HUVECs cultivated with the extract of positively transformed bacteria was inhibited significantly compared with other groups (Pā€‰<ā€‰0. 05). The quality of life of mice in group c was better than in group a and b. The recombinant Bifidobacterium infantis containing pTRKH2-PsT/sKDR plasmid enhanced the efficacy of tumor growth suppression and prolongation of survival, increased the necrosis rate of tumor significantly, and could obviously decrease MVD and the signals of blood flow in tumors.

Conclusion

The Bifidobacterium infantis-mediated sKDR prokaryotic expression system was constructed successfully. This system could express sKDR at gene and protein levels and significantly inhibit the growth of HUVECs induced by VEGF in vitro. Moreover, it could inhibit tumor growth and safely prolong the survival time of LLC C57BL/6 mice.