Basic Study
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jan 28, 2017; 23(4): 603-613
Published online Jan 28, 2017. doi: 10.3748/wjg.v23.i4.603
Suppression of colorectal tumorigenesis by recombinant Bacteroides fragilis enterotoxin-2 in vivo
You Lv, Tao Ye, Hui-Peng Wang, Jia-Ying Zhao, Wen-Jie Chen, Xin Wang, Chen-Xia Shen, Yi-Bin Wu, Yuan-Kun Cai
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 5th People’s Hospital of Shanghai, Fudan University, Shanghai 200240, China
Author contributions: Lv Y, Ye T, Wang HP, Zhao JY, Wang X and Cai YK designed the research; Lv Y, Chen WJ and Wu YB performed the research; Lv Y and Zhao JY contributed new reagents or analytic tools; Lv Y, Wang X and Shen CX analyzed the data; Lv Y and Wang HP wrote the paper.
Supported by the Scientific Research Project of Shanghai Health and Family Planning, and the Commission and the 5th People’s Hospital of Shanghai, Fudan University under Grant No. 201440505.
Institutional review board statement: The study was reviewed and approved by the 1990 Animal Experimental Ethics Committee of East China Normal University Institutional Review Board.
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Animal Care and Use Committee of the Animal Center of the Institute of Biomedical Laboratory of the East China Normal University (IACUC Protocol No. M20150503).
Conflict-of-interest statement: To the best of our knowledge, no conflict of interest exists.
Data sharing statement: Technical appendix, statistical code, and dataset available from the corresponding author at Participants gave informed consent for data sharing.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Correspondence to: Yuan-Kun Cai, MD, Associate Professor, Chief Surgeon of General Surgery, Department of General Surgery, The 5th People’s Hospital of Shanghai, Fudan University, 801 Heqing Road, Shanghai 200240, China.
Telephone: +86-21-64307611 Fax: +86-21-64307611
Received: September 11, 2016
Peer-review started: September 12, 2016
First decision: November 9, 2016
Revised: November 19, 2016
Accepted: December 8, 2016
Article in press: December 8, 2016
Published online: January 28, 2017

To evaluate the impact of recombinant Bacteroides fragilis enterotoxin-2 (BFT-2, or Fragilysin) on colorectal tumorigenesis in mice induced by azoxymethane/dextran sulfate sodium (AOM/DSS).


Recombinant proBFT-2 was expressed in Escherichia coli strain Rosetta (DE3) and BFT-2 was obtained and tested for its biological activity via colorectal 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.


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 ± 0.68 vs 23.23 ± 0.91, P < 0.05) and the ADHT group (21.82 ± 0.68 vs 23.57 ± 1.06, P < 0.05). More tumors were found in the AD group than in the ADLT and ADHT groups (19.75 ± 3.30 vs 6.50 ± 1.73, P < 0.05; 19.75 ± 3.30 vs 6.00 ± 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).


Oral administration with lower-dose biologically active recombinant BFT-2 inhibited colorectal tumorigenesis in mice.

Keywords: Colorectal neoplasms, Bacteroides fragilis toxin, Fragilysin, Recombinant proteins, Mice

Core tip:Bacteroides fragilis enterotoxin-2 (BFT-2) has been considered to promote the development of colorectal cancer (CRC). In this study, we obtained the biologically active recombinant BFT-2 in vitro and found that lower-dose of biologically active BFT-2 could inhibit colorectal tumor formation via the route of intra-gastric administration in a mice model of CRC, which manifested to inhibit cell proliferation and promoted apoptosis. The specific mechanism is still unknown but the findings provide some insights into prevention and treatment of CRC as an intestinal mucosal vaccine.