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Omeprazole promotes carcinogenesis of fore-stomach in mice with co-stimulation of nitrosamine

OBJECTIVES: To investigate if oral omeprazole application induces cancers of fore and glandular stomach in mice. METHODS: A total of 66 eligible male mice were randomly divided into 6 groups, which were treated with control reagent, low (6 mg/kg) and high dose omeprazole (30 mg/kg), N-methyl-N’-nitr...

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Autores principales: Huang, Lei, Qi, Dong-Jiang, He, Wei, Xu, A-Man
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5642558/
https://www.ncbi.nlm.nih.gov/pubmed/29050283
http://dx.doi.org/10.18632/oncotarget.19696
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author Huang, Lei
Qi, Dong-Jiang
He, Wei
Xu, A-Man
author_facet Huang, Lei
Qi, Dong-Jiang
He, Wei
Xu, A-Man
author_sort Huang, Lei
collection PubMed
description OBJECTIVES: To investigate if oral omeprazole application induces cancers of fore and glandular stomach in mice. METHODS: A total of 66 eligible male mice were randomly divided into 6 groups, which were treated with control reagent, low (6 mg/kg) and high dose omeprazole (30 mg/kg), N-methyl-N’-nitro-N-nitrosoguanidine (MNNG, 100 mg/L water), and MNNG plus low and high dose omeprazole, respectively. After 24 weeks, concentrations of acid phosphatase (ACP) and N-acetyl-β-D-glucosaminidase(NAG) in serum and spleen was examined, and p21 and mTOR levels in stomach were detected. RESULTS: The mouse spleen weight index was smaller in the omeprazole group than the control group, and in the MNNG plus omeprazole groups than the MNNG group. In the fore-stomach, more carcinomas were observed in the MNNG plus omeprazole groups than in the MNNG group. In the glandular stomach, there existed more atypical hyperplasia cases in the MNNG plus omeprazole groups than the MNNG-treated group, and one carcinoma was induced in the MNNG plus high dose omeprazole group. Omeprazole alone caused minor gastric pathological changes. Omeprazole treatment lowered both serum and spleen ACP and NAG levels in both the non-MNNG-treated and MNNG-treated subgroups. In fore-stomach, there existed decreased p21 and mTOR levels in the omeprazole-treated groups than in the control group, and in the MNNG plus omeprazole groups than the MNNG-treated group. CONCLUSION: Omeprazole promotes carcinogenesis of the mouse fore-stomach but not the glandular stomach following treatment with MNNG. Lysosomal hydrolase activity was inhibited and some cancer-associated proteins was dysregulated, which requires further explorations.
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spelling pubmed-56425582017-10-18 Omeprazole promotes carcinogenesis of fore-stomach in mice with co-stimulation of nitrosamine Huang, Lei Qi, Dong-Jiang He, Wei Xu, A-Man Oncotarget Research Paper OBJECTIVES: To investigate if oral omeprazole application induces cancers of fore and glandular stomach in mice. METHODS: A total of 66 eligible male mice were randomly divided into 6 groups, which were treated with control reagent, low (6 mg/kg) and high dose omeprazole (30 mg/kg), N-methyl-N’-nitro-N-nitrosoguanidine (MNNG, 100 mg/L water), and MNNG plus low and high dose omeprazole, respectively. After 24 weeks, concentrations of acid phosphatase (ACP) and N-acetyl-β-D-glucosaminidase(NAG) in serum and spleen was examined, and p21 and mTOR levels in stomach were detected. RESULTS: The mouse spleen weight index was smaller in the omeprazole group than the control group, and in the MNNG plus omeprazole groups than the MNNG group. In the fore-stomach, more carcinomas were observed in the MNNG plus omeprazole groups than in the MNNG group. In the glandular stomach, there existed more atypical hyperplasia cases in the MNNG plus omeprazole groups than the MNNG-treated group, and one carcinoma was induced in the MNNG plus high dose omeprazole group. Omeprazole alone caused minor gastric pathological changes. Omeprazole treatment lowered both serum and spleen ACP and NAG levels in both the non-MNNG-treated and MNNG-treated subgroups. In fore-stomach, there existed decreased p21 and mTOR levels in the omeprazole-treated groups than in the control group, and in the MNNG plus omeprazole groups than the MNNG-treated group. CONCLUSION: Omeprazole promotes carcinogenesis of the mouse fore-stomach but not the glandular stomach following treatment with MNNG. Lysosomal hydrolase activity was inhibited and some cancer-associated proteins was dysregulated, which requires further explorations. Impact Journals LLC 2017-07-31 /pmc/articles/PMC5642558/ /pubmed/29050283 http://dx.doi.org/10.18632/oncotarget.19696 Text en Copyright: © 2017 Huang et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Huang, Lei
Qi, Dong-Jiang
He, Wei
Xu, A-Man
Omeprazole promotes carcinogenesis of fore-stomach in mice with co-stimulation of nitrosamine
title Omeprazole promotes carcinogenesis of fore-stomach in mice with co-stimulation of nitrosamine
title_full Omeprazole promotes carcinogenesis of fore-stomach in mice with co-stimulation of nitrosamine
title_fullStr Omeprazole promotes carcinogenesis of fore-stomach in mice with co-stimulation of nitrosamine
title_full_unstemmed Omeprazole promotes carcinogenesis of fore-stomach in mice with co-stimulation of nitrosamine
title_short Omeprazole promotes carcinogenesis of fore-stomach in mice with co-stimulation of nitrosamine
title_sort omeprazole promotes carcinogenesis of fore-stomach in mice with co-stimulation of nitrosamine
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5642558/
https://www.ncbi.nlm.nih.gov/pubmed/29050283
http://dx.doi.org/10.18632/oncotarget.19696
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