title: Suppression of colorectal tumorigenesis by recombinantBacteroides fragilisenterotoxin-2in vivo.
abstract: OBJECTIVE
  To evaluate the impact of recombinantBacteroides fragilisenterotoxin-2 (BFT-2, or Fragilysin) on colorectal tumorigenesis in mice induced by azoxymethane/dextran sulfate sodium (AOM/DSS).
  
  
  METHODS
  Recombinant proBFT-2 was expressed inEscherichia colistrain Rosetta (DE3) and BFT-2 was obtained and tested for its biological activityviacolorectal adenocarcinoma cell strains SW-480. Seventy C57BL/6J mice were randomly divided into a blank (BC;n= 10), model (AD;n= 20), model + low-dose toxin (ADLT;n= 20, 10 μg), and a model + high-dose toxin (ADHT;n= 20, 20 μg) group. Mice weight, tumor formation and pathology were analyzed. Immunohistochemistry determined Ki-67 and Caspase-3 expression in normal and tumor tissues of colorectal mucosa.
  
  
  RESULTS
  Recombinant BFT-2 was successfully obtained, along with its biological activity. The most obvious weight loss occurred in the AD group compared with the ADLT group (21.82 ± 0.68vs23.23 ± 0.91,P< 0.05) and the ADHT group (21.82 ± 0.68vs23.57 ± 1.06,P< 0.05). More tumors were found in the AD group than in the ADLT and ADHT groups (19.75 ± 3.30vs6.50 ± 1.73,P< 0.05; 19.75 ± 3.30vs6.00 ± 2.16,P< 0.05). Pathology showed that 12 mice had adenocarcinoma and 6 cases had adenoma in the AD group. Five mice had adenocarcinoma and 15 had adenoma in the ADLT group. Four mice had adenocarcinoma and 16 had adenoma in the ADHT group. The incidence of colorectal adenocarcinoma in both the ADHT group and the ADHT group was reduced compared to that in the AD group (P< 0.05,P< 0.05). The positive rate of Ki-67 in the ADLT group and the ADHT group was 50% and 40%, respectively, both of which were lower than that found in the AD group (94.44%,P< 0.05,P< 0.05). Caspase-3 expression in the ADLT group and the ADHT group was 45% and 55%, both of which were higher than that found in the BC group (16.67%,P< 0.05,P< 0.05).
  
  
  CONCLUSIONS
  Oral administration with lower-dose biologically active recombinant BFT-2 inhibited colorectal tumorigenesis in mice.
authors.affiliation: You Lv, Tao Ye, Hui-Peng Wang, Jia-Ying Zhao, Wen-Jie Chen, Xin Wang, Chen-Xia Shen, Yi-Bin Wu, Yuan-Kun Cai, Department of General Surgery, The 5 People's Hospital of Shanghai, Fudan University, Shanghai 200240, China.
authors.forename: You
authors.initials: Y
authors.lastname: Lv
authors.affiliation: You Lv, Tao Ye, Hui-Peng Wang, Jia-Ying Zhao, Wen-Jie Chen, Xin Wang, Chen-Xia Shen, Yi-Bin Wu, Yuan-Kun Cai, Department of General Surgery, The 5 People's Hospital of Shanghai, Fudan University, Shanghai 200240, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Ye
authors.affiliation: You Lv, Tao Ye, Hui-Peng Wang, Jia-Ying Zhao, Wen-Jie Chen, Xin Wang, Chen-Xia Shen, Yi-Bin Wu, Yuan-Kun Cai, Department of General Surgery, The 5 People's Hospital of Shanghai, Fudan University, Shanghai 200240, China.
authors.forename: Hui-Peng
authors.initials: HP
authors.lastname: Wang
authors.affiliation: You Lv, Tao Ye, Hui-Peng Wang, Jia-Ying Zhao, Wen-Jie Chen, Xin Wang, Chen-Xia Shen, Yi-Bin Wu, Yuan-Kun Cai, Department of General Surgery, The 5 People's Hospital of Shanghai, Fudan University, Shanghai 200240, China.
authors.forename: Jia-Ying
authors.initials: JY
authors.lastname: Zhao
authors.affiliation: You Lv, Tao Ye, Hui-Peng Wang, Jia-Ying Zhao, Wen-Jie Chen, Xin Wang, Chen-Xia Shen, Yi-Bin Wu, Yuan-Kun Cai, Department of General Surgery, The 5 People's Hospital of Shanghai, Fudan University, Shanghai 200240, China.
authors.forename: Wen-Jie
authors.initials: WJ
authors.lastname: Chen
authors.affiliation: You Lv, Tao Ye, Hui-Peng Wang, Jia-Ying Zhao, Wen-Jie Chen, Xin Wang, Chen-Xia Shen, Yi-Bin Wu, Yuan-Kun Cai, Department of General Surgery, The 5 People's Hospital of Shanghai, Fudan University, Shanghai 200240, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.affiliation: You Lv, Tao Ye, Hui-Peng Wang, Jia-Ying Zhao, Wen-Jie Chen, Xin Wang, Chen-Xia Shen, Yi-Bin Wu, Yuan-Kun Cai, Department of General Surgery, The 5 People's Hospital of Shanghai, Fudan University, Shanghai 200240, China.
authors.forename: Chen-Xia
authors.initials: CX
authors.lastname: Shen
authors.affiliation: You Lv, Tao Ye, Hui-Peng Wang, Jia-Ying Zhao, Wen-Jie Chen, Xin Wang, Chen-Xia Shen, Yi-Bin Wu, Yuan-Kun Cai, Department of General Surgery, The 5 People's Hospital of Shanghai, Fudan University, Shanghai 200240, China.
authors.forename: Yi-Bin
authors.initials: YB
authors.lastname: Wu
authors.affiliation: You Lv, Tao Ye, Hui-Peng Wang, Jia-Ying Zhao, Wen-Jie Chen, Xin Wang, Chen-Xia Shen, Yi-Bin Wu, Yuan-Kun Cai, Department of General Surgery, The 5 People's Hospital of Shanghai, Fudan University, Shanghai 200240, China.
authors.forename: Yuan-Kun
authors.initials: YK
authors.lastname: Cai
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001397:Azoxymethane; D001441:Bacteroides fragilis; D001835:Body Weight; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000139:chemically induced / Q000382:microbiology / Q000628:therapy*; D016264:Dextran Sulfate; D006801:Humans; D007150:Immunohistochemistry; D007422:Intestines / Q000382:microbiology* / Q000473:pathology; D019394:Ki-67 Antigen / Q000378:metabolism; D008666:Metalloendopeptidases / Q000008:administration & dosage*; D051379:Mice; D008810:Mice, Inbred C57BL; D011994:Recombinant Proteins / Q000008:administration & dosage
chemical_list: D019394:Ki-67 Antigen; D011994:Recombinant Proteins; D016264:Dextran Sulfate; D053148:Caspase 3; D008666:Metalloendopeptidases; C091198:fragilysin; D001397:Azoxymethane
keywords: Bacteroides fragilis toxin; Colorectal neoplasms; Fragilysin; Mice; Recombinant proteins