title: Bifidobacteria Expressing Tumstatin Protein for Antitumor Therapy in Tumor-Bearing Mice.
abstract: Tumstatin (Tum) is a powerful angiostatin that inhibits proliferation and induces apoptosis of tumorous vascular endothelial cells. A nonpathogenic and anaerobic bacterium, Bifidobacterium longum (BL), selectively localizes to and proliferates in the hypoxia location within solid tumor. The aims of this study were to develop a novel delivery system for Tum using engineered Bifidobacterium and to investigate the inhibitory effect of Tum on tumor in mice. A vector that enabled the expression of Tum under the control of the pBBADs promoter of BL was constructed and transformed into BL NCC2705 by electroporation. The mouse colon carcinoma cells CT26 (1 × 10(7)/mL) were subcutaneously inserted in the left armpit of BALB/c mice. The tumor-bearing mice were treated with Tum-transformed BL, and green fluorescent protein (GFP)-transformed BL was used as a negative control. The microvessel density (MVD) in the transplanted tumor was determined, and terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate nick end labeling was used to detect apoptosis of vascular endothelial cells in transplanted tumor. The in vitro expression of Tum was examined in BL after l-arabinose induction. Bifidobacterium longum with pBBAD-Tum (BL-Tum) showed significant antitumor effect in tumor-bearing mice. The weight, volume, growth, and MVD, as well as the percentage of apoptotic vascular endothelial cells of transplanted tumors in the tumor-bearing mice treated with Tum-transformed BL were all significantly lower than those in the GFP negative control group. Intragastric administration, injection in tumor and vena caudalis injection of Tum-transformed BL exerted marked antitumor effects in tumor-bearing mice. This is the first demonstration of the utilization of Tum-transformed BL as a specific gene delivery system for treating tumor.
authors.affiliation: Department of Gastroenteroloy, Jinan University of Medical Sciences, Shenzhen Municipal People's Hospital, Shenzhen animal genetic engineering technology research and Development Center, Shenzhen, Guangdong Province, China.
authors.forename: C
authors.initials: C
authors.lastname: Wei
authors.affiliation: Department of Gastroenterology, Peking University Shenzhen Hospital, Shenzhen, Guangdong Province, China.
authors.forename: A Y
authors.initials: AY
authors.lastname: Xun
authors.affiliation: Department of Infectious Diseases, Xinxiang Medical College, Xinxiang, Guangdong Province, China.
authors.forename: X X
authors.initials: XX
authors.lastname: Wei
authors.affiliation: Department of Gastroenteroloy, Jinan University of Medical Sciences, Shenzhen Municipal People's Hospital, Shenzhen animal genetic engineering technology research and Development Center, Shenzhen, Guangdong Province, China.
authors.forename: J
authors.initials: J
authors.lastname: Yao
authors.affiliation: Department of General Surgery, Shenzhen Children's Hospital, Shenzhen, Guangdong Province, China.
authors.forename: J Y
authors.initials: JY
authors.lastname: Wang
authors.affiliation: Department of Gastroenteroloy, Jinan University of Medical Sciences, Shenzhen Municipal People's Hospital, Shenzhen animal genetic engineering technology research and Development Center, Shenzhen, Guangdong Province, China.
authors.forename: R Y
authors.initials: RY
authors.lastname: Shi
authors.affiliation: Department of Gastroenteroloy, Jinan University of Medical Sciences, Shenzhen Municipal People's Hospital, Shenzhen animal genetic engineering technology research and Development Center, Shenzhen, Guangdong Province, China.
authors.forename: G H
authors.initials: GH
authors.lastname: Yang
authors.affiliation: Department of Gastroenteroloy, Jinan University of Medical Sciences, Shenzhen Municipal People's Hospital, Shenzhen animal genetic engineering technology research and Development Center, Shenzhen, Guangdong Province, China.
authors.forename: Y X
authors.initials: YX
authors.lastname: Li
authors.affiliation: Department of Gastroenteroloy, Jinan University of Medical Sciences, Shenzhen Municipal People's Hospital, Shenzhen animal genetic engineering technology research and Development Center, Shenzhen, Guangdong Province, China.
authors.forename: Z L
authors.initials: ZL
authors.lastname: Xu
authors.affiliation: Department of Gastroenteroloy, Jinan University of Medical Sciences, Shenzhen Municipal People's Hospital, Shenzhen animal genetic engineering technology research and Development Center, Shenzhen, Guangdong Province, China.
authors.forename: M G
authors.initials: MG
authors.lastname: Lai
authors.affiliation: Department of Gastroenteroloy, Jinan University of Medical Sciences, Shenzhen Municipal People's Hospital, Shenzhen animal genetic engineering technology research and Development Center, Shenzhen, Guangdong Province, China.
authors.forename: R
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Department of Gastroenteroloy, Jinan University of Medical Sciences, Shenzhen Municipal People's Hospital, Shenzhen animal genetic engineering technology research and Development Center, Shenzhen, Guangdong Province, China wangls168@163.com.
authors.forename: L-S
authors.initials: LS
authors.lastname: Wang
authors.affiliation: Department of Cell Biology, Southern Medical University, Guangzhou, Guangdong Province, China.
authors.forename: W S
authors.initials: WS
authors.lastname: Zeng
mesh_terms: D000818:Animals; D001324:Autoantigens / Q000008:administration & dosage* / Q000235:genetics; D000069978:Bifidobacterium longum; D024141:Collagen Type IV / Q000008:administration & dosage* / Q000235:genetics; D004195:Disease Models, Animal; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009374:Neoplasms, Experimental / Q000473:pathology*
chemical_list: D001324:Autoantigens; D024141:Collagen Type IV; C057112:type IV collagen alpha3 chain
keywords: Bifidobacterium; tumor-bearing mice; tumstatin