Bifidobacterium longum as a delivery system of TRAIL and endostatin cooperates with chemotherapeutic drugs to inhibit hypoxic tumor growth.
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.
Hu
B
B
Department of Biological Science and Technology and State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, China.
Kou
L
L
Li
C
C
Zhu
L-P
LP
Fan
Y-R
YR
Wu
Z-W
ZW
Wang
J-J
JJ
Xu
G-X
GX
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage; D017209:Apoptosis / Q000187:drug effects; D001644:Bifidobacterium / Q000502:physiology*; D001859:Bone Neoplasms / Q000473:pathology / Q000628:therapy*; D003131:Combined Modality Therapy; D004317:Doxorubicin / Q000008:administration & dosage*; D016503:Drug Delivery Systems / Q000379:methods*; D043169:Endostatins / Q000008:administration & dosage* / Q000235:genetics; D008297:Male; D051379:Mice; D012516:Osteosarcoma / Q000473:pathology / Q000628:therapy*; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000235:genetics; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000008:administration & dosage* / Q000737:chemistry / Q000235:genetics; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D043169:Endostatins; D011994:Recombinant Proteins; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D004317:Doxorubicin