Basic Study
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Oct 15, 2021; 13(10): 1518-1531
Published online Oct 15, 2021. doi: 10.4251/wjgo.v13.i10.1518
Survival effect of probiotics in a rat model of colorectal cancer treated with capecitabine
Graciela Gigola, Pedro Carriere, María Belén Novoa Díaz, Gabriela Perdigon, Ariel Osvaldo Zwenger, Claudia Gentili
Graciela Gigola, Pedro Carriere, María Belén Novoa Díaz, Claudia Gentili, Biología, Bioquímica y Farmacia, Universidad Nacional del Sur (UNS)- INBIOSUR (CONICET-UNS), Bahía Blanca 8000, Buenos Aires Provincia, Argentina
Gabriela Perdigon, [CERELA] Centro de referencia para lactobacilos - [CCT CONICET NOA SUR], San Miguel de Tucumán 4000, Argentina
Ariel Osvaldo Zwenger, Centro de Estudios Clínicos SAGA, CEC SAGA, Santiago de Chile 8320000, Chile
Author contributions: Gigola G, Carriere P, Perdigón G and Zwenger AO explained the term; Gigola G, Perdigón G and Zwenger AO contributed to methodology, investigation and formal analysis; Gigola G, Carriere P, Novoa Diaz MB and Gentili C drafted the original manuscript; Gigola G and Gentili C reviewed and re-edited the manuscript; Gigola G and Zwenger AO received the financial support; all authors contributed to the conceptualization and visualization of this manuscript.
Supported by Universidad Nacional del Sur, Argentina, No. PGI 24/B138, No. PGI 24/ZB50, and No. PGI 24/ZB63.
Institutional review board statement: The study was evaluated and approved by a committee of experts on the subject conformed by members of the Department of Biology, Biochemistry and Pharmacy of the National University of the South.
Institutional animal care and use committee statement: All the animals employed in the experiments were under controlled conditions and the activities were supervised by a veterinarian in charge, in accordance with the principles of care and use of laboratory animals. The experimental design was evaluated and approved by experts on the subject and certified by the Department of Post-Graduate Studies the National University of the South.
Conflict-of-interest statement: The authors declare that they have no competing interests.
Data sharing statement: No additional data are available.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (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:
Corresponding author: Graciela Gigola, PhD, Doctor, Professor, Biología, Bioquímica y Farmacia, Universidad Nacional del Sur (UNS)- INBIOSUR (CONICET-UNS), San Juan 670, Bahía Blanca 8000, Buenos Aires Provincia, Argentina.
Received: April 27, 2021
Peer-review started: April 27, 2021
First decision: June 13, 2021
Revised: June 26, 2021
Accepted: August 27, 2021
Article in press: August 27, 2021
Published online: October 15, 2021
Research background

Colorectal cancer (CRC) is one of the leading causes of mortality due to malignant diseases worldwide. Capecitabine, the prodrug of 5-fluorouracil (5-FU), is one of the most important chemotherapeutic agents used in CRC treatment. Prolonged use of regimens containing capecitabine can lead to systemic toxicity with the consequent discontinuation of the treatment.

Research motivation

To improve the management of CRC patients, it is necessary the incorporation of therapies that mitigate the side effects of the conventional CRC treatment and reduce its resistance. Probiotics have beneficial properties when they are used in the management of many gastrointestinal diseases. Also, it is known that probiotics are able to reduce undesirable effects of 5-FU in CRC patients and to benefit CRC patients treated surgically. In a rat CRC model, probiotic supplementation potentiated the antitumor effect of 5-FU chemotherapy on colon. The positive impact of probiotics in a preclinical model of CRC under capecitabine treatment was unknown when we started our experimental work.

Research objectives

The aim of this study was to evaluate the impact of a mixture of probiotics strains in the outcome of a rat CRC model treated with capecitabine and monitored until the end of life.

Research methods

Male Wistar-Lewis rats with CRC induced by 1,2-dimethylhydrazine dihydrochloride (1,2-DMH) were grouped as follow: 1.2-DMH alone (DMH group, n = 10), 1,2-DMH + capecitabine (DMH-C group, n = 10), 1,2-DMH + probiotics (DMH-P group, n = 10), 1,2-DMH + capecitabine + probiotics (DMH-C-P group, n = 10). Two groups of male Wistar-Lewis rats were used as controls: untreated group (Control n = 5) and Control + probiotics group (Control-P, n = 5). During the experiment, the following were analyzed in all groups: survival time, clinicopathological characteristics, quality of life and cause of death.

Research results

The administration of probiotics showed a benefit in survival time, weight gain, clinical manifestations and cancer development.

Research conclusions

The fact that the animals were followed until the end of life allow to conclude that this study is the first that shows the positive impact of probiotics in the overall survival of rats with CRC under capecitabine treatment.

Research perspectives

The use of probiotics could improve the overall survival and quality of life of patients with CRC treated with capecitabine.