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BMC Cancer ; 18(1): 1111, 2018 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-30424722

RESUMO

BACKGROUND: Colorectal cancer has been found to be attenuated either with prophylactic manipulation of gut microbiome with probiotics or celecoxib, a non-steroidal anti-inflammatory drug mainly by suppressing early pro-carcinogenic markers in various experimental studies. Therefore, the present study was designed to assess the prophylactic potential of combinatorial administration of probiotics (Lactobacillus rhamnosus GG, Lactobacillus acidophilus) and celecoxib in experimental colon carcinogenesis. METHODS: Six groups of Spraugue Dawely rats received probiotics L.rhamnosus GG or/and L.acidophilus in combination with celecoxib one week prior to the inducement of tumor by 1,2-dimethylhydrazine (DMH) and the treatment continued for 18 weeks. Prophylactic potentials of probiotics and celecoxib were determined by employing various methods such as tumor incidence, tumor burden, tumor multiplicity, apoptosis, caspase activity, expression of proto-oncogene K-ras and tumor suppressor p53 gene in colonic tumors. RESULTS: Interestingly, it was found that one week prior supplementation of both probiotics and celecoxib reduced tumor burden, tumor multiplicity, down-regulated the expression of anti-apoptotic Bcl-2, proto-oncogene K-ras and up-regulated pro-apoptotic Bax as well as tumor suppressor p53 in L.rhamnosus GG + celecoxib+DMH animals compared with counter controls and DMH-treated. CONCLUSIONS: It can be concluded that such combinatorial approach may be useful in reducing the burden and severity of disease in highly susceptible individuals but needs to be validated clinically.


Assuntos
Celecoxib/farmacologia , Neoplasias Colorretais/dietoterapia , Lacticaseibacillus rhamnosus , Lactobacillus acidophilus , Probióticos/administração & dosagem , 1,2-Dimetilidrazina/toxicidade , Animais , Apoptose/efeitos dos fármacos , Carcinogênese/efeitos dos fármacos , Carcinogênese/patologia , Carcinógenos/toxicidade , Celecoxib/uso terapêutico , Colo/efeitos dos fármacos , Colo/patologia , Neoplasias Colorretais/induzido quimicamente , Neoplasias Colorretais/patologia , Neoplasias Colorretais/prevenção & controle , Terapia Combinada/métodos , Regulação para Baixo/efeitos dos fármacos , Avaliação Pré-Clínica de Medicamentos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Masculino , Neoplasias Experimentais/induzido quimicamente , Neoplasias Experimentais/dietoterapia , Neoplasias Experimentais/prevenção & controle , Proto-Oncogene Mas , Ratos , Ratos Sprague-Dawley , Resultado do Tratamento , Regulação para Cima/efeitos dos fármacos , Proteína X Associada a bcl-2/metabolismo
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