Oncotarget

Research Papers:

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

Lei Huang, Dong-Jiang Qi, Wei He and A-Man Xu _

PDF  |  HTML  |  How to cite

Oncotarget. 2017; 8:70332-70344. https://doi.org/10.18632/oncotarget.19696

Metrics: PDF 1843 views  |   HTML 2291 views  |   ?  


Abstract

Lei Huang1,*, Dong-Jiang Qi1,2,*, Wei He1,2 and A-Man Xu1,2

1Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, China

2Department of General Surgery, The Fourth Affiliated Hospital of Anhui Medical University, Hefei, China

*Lei Huang and Dong-Jiang Qi contributed equally to this work

Correspondence to:

A-Man Xu, email: [email protected]

Lei Huang, email: [email protected]

Keywords: proton pump inhibitor, MNNG, carcinogenesis, lysosomal enzyme, randomized study

Received: August 02, 2016     Accepted: June 19, 2017     Published: July 31, 2017

ABSTRACT

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.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.
PII: 19696