Copyright
©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
Infliximab does not increase colonic cancer risk associated to murine chronic colitis
Loris R Lopetuso, Valentina Petito, Tiziano Zinicola, Cristina Graziani, Viviana Gerardi, Vincenzo Arena, Maria Emiliana Caristo, Andrea Poscia, Giovanni Cammarota, Alfredo Papa, Valerio Cufino, Alessandro Sgambato, Antonio Gasbarrini, Franco Scaldaferri
Loris R Lopetuso, Valentina Petito, Tiziano Zinicola, Cristina Graziani, Viviana Gerardi, Giovanni Cammarota, Alfredo Papa, Valerio Cufino, Antonio Gasbarrini, Franco Scaldaferri, Gastroenterology Division, Catholic University of Sacred Heart, 00168 Rome, Italy
Vincenzo Arena, Institute of Pathology, Catholic University of Sacred Heart, 00168 Rome, Italy
Maria Emiliana Caristo, Experimental Center, Catholic University of Sacred Heart, 00168 Rome, Italy
Andrea Poscia, Institute of Hygiene, Catholic University of Sacred Heart, 00168 Rome, Italy
Alessandro Sgambato, Institute of General Pathology, Catholic University of Sacred Heart, 00168 Rome, Italy
Author contributions: Lopetuso LR did most of research and writing; Petito V performed samples processing and in vitro analysis; Arena V performed histological and tumor analysis; Zinicola T, Graziani C, Gerardi V assisted with writing; Caristo ME and Poscia A performed the statistical analysis; Cammarota G, Papa A and Cufino V assisted with the editing; Sgambato A, Gasbarrini A and Scaldaferri F conceived the original concept, assisted with the research and performed the critical revision of the manuscript; Lopetuso LR, Petito V, Gasbarrini A and Scaldaferri F contributed equally to this work.
Supported by Crohn’s and Colitis Foundation of America, Research Fellowship Award, No. CON125252 (to Lopetuso LR); European Crohn’s and Colitis Organization Grant (to Scaldaferri F); Società Italiana di Gastroenterologia prize (to Scaldaferri F).
Institutional review board statement: The study was reviewed and approved by the Catholic University Institutional Review Board.
Institutional animal care and use committee statement: All experiments were approved by the Local Ethics Committee for Animal Research Studies at the Catholic University of Rome (protocol number F42/2009).
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 francoscaldaferri@gmail.com.
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: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Dr. Franco Scaldaferri, Gastroenterology Division, Catholic University of Sacred Heart, Largo Gemelli 8, 00168 Rome, Italy.
francoscaldaferri@gmail.com
Telephone: +39-6-30156018 Fax: +39-6-30156018
Received: June 27, 2016
Peer-review started: June 27, 2016
First decision: July 29, 2016
Revised: August 23, 2016
Accepted: September 14, 2016
Article in press: September 14, 2016
Published online: November 28, 2016
Processing time: 152 Days and 11.1 Hours
AIM
To explore the influence of Infliximab (IFX) on cancer progression in a murine model of colonic cancer associated to chronic colitis.
METHODS
AOM/DSS model was induced in C57BL/6 mice. Mice were injected with IFX (5 mg/kg) during each DSS cycle while control mice received saline. Body weight, occult blood test and stool consistency were measured to calculate the disease activity index (DAI). Mice were sacrificed at week 10 and colons were analyzed macroscopically and microscopically for number of cancers and degree of inflammation. MTT assay was performed on CT26 to evaluate the potential IFX role on metabolic activity and proliferation. Cells were incubated with TNF-α or IFX or TNF-α plus IFX, and cell vitality was evaluated after 6, 24 and 48 h. The same setting was used after pre-incubation with TNF-α for 24 h.
RESULTS
IFX significantly reduced DAI and body weight loss in mice compared with controls, preserving also colon length at sacrifice. Histological score was also reduced in treated mice. At macroscopic analysis, IFX treated mice showed a lower number of tumor lesions compared to controls. This was confirmed at microscopic analysis, although differences were not statistically significant. In vitro, IFX treated CT26 maintained similar proliferation ability at MTT test, both when exposed to IFX alone and when associated to TNF-α.
CONCLUSION
IFX did not increase colonic cancer risk in AOM-DSS model of cancer on chronic colitis nor influence directly the proliferation of murine colon cancer epithelial cells.
Core tip: We report our results on the potential role of Infliximab on cancer progression in AOM-DSS murine model of colorectal cancer associated to chronic colitis. AOM/DSS model was induced in C57BL/6 mice. Mice were injected with Infliximab during each DSS cycle while control mice received saline. Mice were sacrificed at week 10 and colons were analyzed macroscopically and microscopically for number of cancers and degree of inflammation. MTT assay was performed on CT26 to evaluate the potential influence of Infliximab (IFX) role on metabolic activity and proliferation. This study demonstrates that beside its well-known healing capacity, IFX does not increase proliferative cancer cells ability and colorectal cancer risk in AOM-DSS model of tumor on chronic colitis.
