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

被引:47
作者
Hu, B. [4 ,5 ]
Kou, L. [4 ,5 ]
Li, C. [4 ,5 ]
Zhu, L-P [4 ,5 ]
Fan, Y-R [3 ]
Wu, Z-W [1 ]
Wang, J-J [4 ,5 ]
Xu, G-X [1 ,2 ]
机构
[1] Nanjing Univ, Ctr Publ Hlth Res, Sch Med, Nanjing 210093, Peoples R China
[2] Jiangsu Prov Res Ctr Gene Pharmaceut Engn & Techn, Suzhou, Peoples R China
[3] Nanjing Univ Sci & Technol, Sch Chem Engn, Nanjing, Peoples R China
[4] Nanjing Univ, Sch Life Sci, Dept Biol Sci & Technol, Nanjing 210093, Peoples R China
[5] Nanjing Univ, Sch Life Sci, State Key Lab Pharmaceut Biotechnol, Nanjing 210093, Peoples R China
基金
中国国家自然科学基金;
关键词
Bifidobacterium longum; TRAIL; endostatin; gene therapy; selective location; synergistic interactions; APOPTOSIS-INDUCING LIGAND; CANCER GENE-THERAPY; SELECTIVE LOCALIZATION; MEDIATED APOPTOSIS; ANTITUMOR-ACTIVITY; UP-REGULATION; KAPPA-B; EXPRESSION; DEATH; RECEPTOR;
D O I
10.1038/cgt.2009.7
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
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. Cancer Gene Therapy (2009) 16, 655-663; doi:10.1038/cgt.2009.7; published online 20 February 2009
引用
收藏
页码:655 / 663
页数:9
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