Survival effect of probiotics in a rat model of colorectal cancer treated with capecitabine

GIGOLA, GRACIELA; CARRIERE PEDRO MATÍAS; NOVOA DÍAZ BELEN; GABRIELA PERDIGON; ZWENGER ARIEL; GENTILI, CLAUDIA

World Journal of Gastrointestinal Oncology

Baishideng Publishing Group

Año: 2021 vol. 13 p. 1518 - 1531

1948-5204

BACKGROUNDProbiotics are used to manage a number of gastrointestinal disorders due to theirbeneficial properties. Clinical reports showed that probiotics also improve the lifequality of patients with colorectal cancer (CRC) subjected to oncologic treatment.In a CRC animal model, probiotics supplementation has the potential to decreasethe formation of aberrant crypts and ameliorate tumor malignancy, enhancing theantitumor effect of 5-fluorouracil (5-FU) chemotherapy. Based on these data, wehypothesize that the administration of probiotics impact positively in the overallsurvival and life quality of rats with CRC under the treatment of capecitabine,which is the pro drug of 5-FU.AIMTo evaluate the probiotics effects in a rat CRC model treated with capecitabineand followed until the end of life.METHODS1,2-Dimethylhidrazine dihydrochloride (1,2-DMH) was employed as carcinogeninductor of CRC. Fifty male Wistar-Lewis rats were randomly assigned to one offive following groups: Control (n = 5), Control + probiotics (Control-P group, n =5), 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) and 1,2-DMH + capecitabine+ probiotics (DMH-C-P group, n = 10). All parametric data were expressed as the mean ± SD. The statistical significance of differences was analyzed usingone-way ANOVA. Data were analyzed with InfoStat software. The results wereconsidered statistically significant at P < 0.05. Overall survival was evaluated withthe Kaplan-Meier estimator with the log-rank test.RESULTSThe data of mean overall survival for DMH, DMH-P, DMH-C, DMH-C-P, Controland Control-P groups were 250 d [95% confidence interval (CI): 242.5-253.1], 268 d(95%CI: 246.3-271.4), 380 d (95%CI: 337.8-421.9), 480 d (95%CI: 436.9-530.7), 588 d(95%CI: 565.8-609.3) and 590 d (95%CI: 564.3-612.9), respectively, with asignificant difference between DMH-C and DMH-C-P groups (P = 0.001).Comparing all groups by Kaplan-Meier estimator, we found a significantlydifferent in the overall survival of DMH and DMH-P groups respect to DMH-C (P= 0.001) and DMH-C-P (P = 0.001) groups; interestingly, there were no meaningfuldifferences between Control, Control-P and DMH-C-P groups (P = 0.012). Thetendency of change in body weight gain of the rats at 90 d of finishing DMHadministration was similar in Control group compared with DMH-C and DMHC-P groups; however, and of relevance, DMH-C-P group has experienced a higherbody weight gain at the end of animal?s life than DMH-C group (P = 0.001). InDMH-C-P group we found a positive effect of probiotics in clinical manifestationssince diarrhea, constipation and blood stool were absenting. Also, the tumorburden was lower in DMH-C-P than DMH-C, DMH-P or DMH groups (1.25 vs1.81 vs 3.9 vs 4.8 cm2, respectively). DMH-C and DMH-C-P groups showed onlymucinous carcinoma type while in other DMH groups the tumor types werevariable. However, mucinous carcinoma from DMH-C-P group showed invasionuntil muscularis propria layer. Interestingly, metastatic lymph node was observedin DMH, DMH-C and DMH-P groups but not in DMH-C-P. All animals inControl group died from natural causes without objective injuries. All animals ofDMH and DMH-P groups died from tumor complications (i.e., obstruction orintestinal perforation); however, this cause was seen only in 44.5% of DMH-C andDMH-C-P groupsCONCLUSIONProbiotics administration improves life quality of rats with CRC under capecitabinetreatment and also has a positive effect in the overall survival of theseanimals treated with this drug.