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.

Gene therapy for cancer: bacteria-mediated anti-angiogenesis therapy

“…44 The main advantage of Bifidobacteria, on the other hand, is that they are non-pathogenic. Li et al 45 successfully used Bifidobacterium adolescentis as a vector for the expression of endostatin within tumors. These authors showed that a strong inhibition of angiogenesis was able to significantly inhibit local tumor growth.…”

A new expression plasmid in Bifidobacterium longum as a delivery system of endostatin for cancer gene therapy

“…The carbohydrates fermentation was determined on TPY broth containing bromocresol purple (0.04 g/l) as a pH indicator, and supplemented with different carbon source. 9 B. longum-pBV22210-Endo and wild-type B. longum were inoculated into the above medium. After anaerobic incubation at 371C for 8 days, they were detected by the color of indicator.…”

“…6 These plasmids, however, could not express foreign gene in Bifidobacterium, which hampered broader application of Bifidobacterium as a specific gene delivery system for cancer gene therapy although successful expressions of foreign gene in the Bifidobacterium have been reported. [7][8][9][10][11] Our previous studies demonstrated that pBV220, an E. coli-derived vector, could express foreign gene in B. adolescentis and B. longum. 9,10 However, it was found to be unstable in Bifidobacterium in the absence of selective antibiotics, which was particularly disadvantageous for prolonged and large-scale cultivation of the plasmid-bearing cells.…”

“…[7][8][9][10][11] Our previous studies demonstrated that pBV220, an E. coli-derived vector, could express foreign gene in B. adolescentis and B. longum. 9,10 However, it was found to be unstable in Bifidobacterium in the absence of selective antibiotics, which was particularly disadvantageous for prolonged and large-scale cultivation of the plasmid-bearing cells. Therefore, in the present study, we developed a shuttle vector, which could replicate in both Escherichia coli and B. longum and expressed a target gene in B. longum.…”

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

“…Though some Bifidobacterium-Escherichia coli shuttle vectors have been constructed in recent years, only some of them expressed foreign genes successfully. [23][24][25][26][27][28][29][30][31][32][33] In our previous studies, we developed a shuttle vector (pBV22210), which could replicate stably and expressed recombinant human endostatin in both E. coli and B. longum. B. longum transfected with pBV22210-endostatin showed a clear inhibitory effect on the growth of mouse solid liver tumor in vivo.…”